Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment ...remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
An overview of Sun–Sky Radiometer Observation Network (SONET) measurements in China is presented. Based on observations at 16 distributed SONET sites in China, atmospheric aerosol parameters are ...acquired via standardization processes of operational measurement, maintenance, calibration, inversion, and quality control implemented since 2010. A climatology study is performed focusing on total columnar atmospheric aerosol characteristics, including optical (aerosol optical depth, ÅngstrÖm exponent, fine-mode fraction, single-scattering albedo), physical (volume particle size distribution), chemical composition (black carbon; brown carbon; fine-mode scattering component, coarse-mode component; and aerosol water), and radiative properties (aerosol radiative forcing and efficiency). Data analyses show that aerosol optical depth is low in the west but high in the east of China. Aerosol composition also shows significant spatial and temporal variations, leading to noticeable diversities in optical and physical property patterns. In west and north China, aerosols are generally affected by dust particles, while monsoon climate and human activities impose remarkable influences on aerosols in east and south China. Aerosols in China exhibit strong light-scattering capability and result in significant radiative cooling effects.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
High-energy photons from the Crab Nebula
The Crab Nebula contains a pulsar that excites the surrounding gas to emit high-energy radiation. The combination of the pulsar's youth and nearby location ...makes the nebula the brightest gamma-ray source in the sky. The LHAASO Collaboration report observations of this source at energies of tera– to peta–electron volts, extending the spectrum of this prototypical object. They combine these data with observations at lower energies to model the physics of the emission process. The multiwave-length data can be explained by a combination of synchrotron radiation and inverse Compton scattering.
Science
, abg5137, this issue p.
425
Detection of the Crab Nebula at peta–electron volt energies constrains the gamma-ray emission mechanism.
The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar’s rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10
−4
to 1.1 peta–electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta–electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron’s size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta–electron volt electrons, 2.5 × 10
36
ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta–electron volt protons to the production of the highest-energy gamma rays.
Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
The iron stable isotope compositions (δ56Fe) and iron valence states of ultrahigh‐pressure eclogites from Bixiling in the Dabie orogen belt, China, were measured to trace the changes of geochemical ...conditions during vertical transportation of earth materials, for example, oxygen fugacity. The bulk Fe3+/ΣFe ratios of retrograde eclogites, determined by Mössbauer spectroscopy, are consistently higher than those of fresh eclogites, suggesting oxidation during retrograde metamorphism and fluid infiltration. The studied eclogites (five samples) display limited mid‐ocean ridge basalts (MORB)‐like (~0.10‰) δ56Fe values, which are indistinguishable from their protoliths, that is, gabbro cumulates formed through differentiation of mantle‐derived basaltic magma. This suggests that Fe isotope fractionation during continental subduction is limited. Garnet separates display limited δ56Fe variation ranging from −0.08 ± 0.07 ‰ to 0.02 ± 0.07‰, whereas coexisting omphacite displays a large variation of δ56Fe values from 0.15 ± 0.07‰ to 0.47 ± 0.07‰. Omphacite also has highly variable Fe3+/ΣFe ratios from 0.367 ± 0.025 to 0.598 ± 0.024, indicating modification after peak metamorphism. Omphacite from retrograde eclogites has elevated Fe3+/ΣFe ratios (0.54–0.60) compared to that from fresh eclogites (~0.37), whereas garnet displays a narrow range of ferric iron content with Fe3+/ΣFe ratios from 0.039 ± 0.013 to 0.065 ± 0.022. The homogenous δ56Fe values and Fe3+/ΣFe ratios of garnet suggest that it survived the retrograde metamorphism and preserved its Fe‐isotopic features and ferric contents of peak metamorphism. Because of similar diffusion rates of Fe and Mg in garnet and omphacite, and constant Δ26Mgomphacite‐garnet values (1.14 ± 0.04‰), equilibrium iron isotope fractionation between garnet and omphacite was probably achieved during peak metamorphism. Elevated Fe3+/ΣFe ratios of omphacite from retrograde eclogites and variant Δ56Feomphacite‐garnet values of the studied eclogites (0.13 ± 0.10‰ to 0.48 ± 0.10‰) indicate that oxidized geofluid infiltration resulted in the elevation of δ56Fe values of omphacite during retrograde metamorphism.
Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory ...(LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.
Aim To investigate the potential of iodine concentration (IC) determined using virtual monochromatic spectral computed tomography (CT) to predict the response of gastric carcinomas to preoperative ...neoadjuvant chemotherapy (NC). Materials and methods A total of 20 patients were enrolled who underwent two spectral CT examinations (1 week before and two cycles after NC). The percentage change in tumour thickness (%ΔCWT) and in IC on the arterial phase (%ΔIC-a) and venous phase (%ΔIC-v) after NC were calculated and compared for different histopathological regression grades and response groups. The diagnostic efficacies to discriminate good response (GR) and poor response (PR) of the above three parameters were evaluated using receiver operating characteristic (ROC) curves. Results The decrease rate of %ΔIC-a for the GR group was higher than that for the PR group (−0.59 −0.76, −0.20 versus −0.11 −0.75, 0.92, p =0.012). There was no significant difference in the %ΔIC-v and %ΔCWT values between the GR and PR groups ( p =0.076 and p =0.779, respectively). The areas under the ROC curve (AUC) values were 0.857, 0.762, and 0.542 for %ΔIC-a, %ΔIC-v, and %ΔCWT, respectively, in the response prediction. The cut-off value for identifying PR was a decrease rate of <52.9% for %ΔIC-a, and the sensitivity and specificity values were 0.857 and 0.833. Conclusion Changes in the IC for gastric carcinomas following NC were detected using spectral CT and correlated with histopathological regression. The prediction efficacy for IC was better than that for tumour thickness, with IC on the arterial phase being a better predictor than IC on the venous phase.
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
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