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.
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).
Weyl semimetals are a class of materials that can be regarded as three-dimensional analogs of graphene upon breaking time-reversal or inversion symmetry. Electrons in a Weyl semimetal behave as Weyl ...fermions, which have many exotic properties, such as chiral anomaly and magnetic monopoles in the crystal momentum space. The surface state of a Weyl semimetal displays pairs of entangled Fermi arcs at two opposite surfaces. However, the existence of Weyl semimetals has not yet been proved experimentally. Here, we report the experimental realization of a Weyl semimetal in TaAs by observing Fermi arcs formed by its surface states using angle-resolved photoemission spectroscopy. Our first-principles calculations, which match remarkably well with the experimental results, further confirm that TaAs is a Weyl semimetal.
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.
Highlights • CP−/− mice and mice that received FAC had high levels of brain iron. • Brain iron accumulation exacerbated TH-positive neurons apoptosis in MPTP-treated mice. • DFO reduced the neuronal ...damage in MPTP-treated CP−/− mice. • Increased oxidative stress was involved in cell apoptosis exacerbated by the increased brain iron.
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.
Double neutron star (DNS) merger events are promising candidates of short gamma-ray burst (sGRB) progenitors as well as high-frequency gravitational wave (GW) emitters. On August 17, 2017, such a ...coinciding event was detected by both the LIGO-Virgo gravitational wave detector network as GW170817 and Gamma-Ray Monitor on board NASA's Fermi Space Telescope as GRB 170817A. Here, we show that the fluence and spectral peak energy of this sGRB fall into the lower portion of the distributions of known sGRBs. Its peak isotropic luminosity is abnormally low. The estimated event rate density above this luminosity is at least Formula: see text Gpc
yr
, which is close to but still below the DNS merger event rate density. This event likely originates from a structured jet viewed from a large viewing angle. There are similar faint soft GRBs in the Fermi archival data, a small fraction of which might belong to this new population of nearby, low-luminosity sGRBs.
MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid ...leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.
Background
Altered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic ...hypersensitivity via peripheral up‐regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC‐derived NGF is still unknown.
Methods
CRL‐2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co‐expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL‐2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined.
Key Results
Transcriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB‐treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB‐treated rats. Meanwhile, a 2.1‐fold increase in co‐expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition.
Conclusions & Inferences
Butyrate‐EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS‐like animal model.
Our study illustrated that butyrate promoted the secretion of NGF from enteric glial cells (EGCs) and contributed to visceral hypersensitivity in rats. The results clarified the potential unignorable source of NGF from EGC and highlighted the important role of EGC in pathogenesis of irritable bowel syndrome (IBS).
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