Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in ...breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH
subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.
Abstract
A recent focus of quantum spin liquid (QSL) studies is how disorder/randomness in a QSL candidate affects its true magnetic ground state. The ultimate question is whether the QSL survives ...disorder or the disorder leads to a “spin-liquid-like” state, such as the proposed random-singlet (RS) state. Since disorder is a standard feature of most QSL candidates, this question represents a major challenge for QSL candidates. YbMgGaO
4
, a triangular lattice antiferromagnet with effective spin-1/2 Yb
3+
ions, is an ideal system to address this question, since it shows no long-range magnetic ordering with Mg/Ga site disorder. Despite the intensive study, it remains unresolved as to whether YbMgGaO
4
is a QSL or in the RS state. Here, through ultralow-temperature thermal conductivity and magnetic torque measurements, plus specific heat and DC magnetization data, we observed a residual
κ
0
/
T
term and series of quantum spin state transitions in the zero temperature limit for YbMgGaO
4
. These observations strongly suggest that a QSL state with itinerant excitations and quantum spin fluctuations survives disorder in YbMgGaO
4
.
Abstract
Object GRB 221009A is the brightest gamma-ray burst (GRB) detected in more than 50 yr of study. In this paper, we present observations in the X-ray and optical domains obtained by the ...GRANDMA Collaboration and the Insight Collaboration. We study the optical afterglow with empirical fitting using the GRANDMA+HXMT-LE data sets augmented with data from the literature up to 60 days. We then model numerically using a Bayesian approach, and we find that the GRB afterglow, extinguished by a large dust column, is most likely behind a combination of a large Milky Way dust column and moderate low-metallicity dust in the host galaxy. Using the GRANDMA+HXMT-LE+XRT data set, we find that the simplest model, where the observed afterglow is produced by synchrotron radiation at the forward external shock during the deceleration of a top-hat relativistic jet by a uniform medium, fits the multiwavelength observations only moderately well, with a tension between the observed temporal and spectral evolution. This tension is confirmed when using the augmented data set. We find that the consideration of a jet structure (Gaussian or power law), the inclusion of synchrotron self-Compton emission, or the presence of an underlying supernova do not improve the predictions. Placed in the global context of GRB optical afterglows, we find that the afterglow of GRB 221009A is luminous but not extraordinarily so, highlighting that some aspects of this GRB do not deviate from the global known sample despite its extreme energetics and the peculiar afterglow evolution.
Multielement solid solution alloys are intrinsically disordered on the atomic scale, and many of their advanced properties originate from the local structural characteristics. The local structure of ...a NiCoCr solid solution alloy is measured with x-ray or neutron total scattering and extended x-ray absorption fine structure (EXAFS) techniques. The atomic pair distribution function analysis does not exhibit an observable structural distortion. However, an EXAFS analysis suggests that the Cr atoms are favorably bonded with Ni and Co in the solid solution alloys. This short-range order (SRO) may make an important contribution to the low values of the electrical and thermal conductivities of the Cr-alloyed solid solutions. In addition, an EXAFS analysis of Ni ion irradiated samples reveals that the degree of SRO in NiCoCr alloys is enhanced after irradiation.
ABSTRACT
The High Energy (HE) X-ray telescope on board the Hard X-ray Modulation Telescope (Insight-HXMT) can serve as a wide field of view (FOV) gamma-ray monitor with high time resolution (μs) and ...large effective area (up to thousands cm2). We developed a pipeline to search for gamma-ray bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with gravitational wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. Fermi/GBM, POLAR). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of Insight-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either Swift/BAT or Fermi/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of Insight-HXMT/HE is increased to about 1.5E-08 erg cm−2 (200 keV–3 MeV). We also used this targeted coherent method to search Insight-HXMT/HE data for electromagnetic counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events.
Abstract
The most fascinating feature of certain two-dimensional (2D) gapless quantum spin liquid (QSL) is that their spinon excitations behave like the fermionic carriers of a paramagnetic metal. ...The spinon Fermi surface is then expected to produce a linear increase of the thermal conductivity with temperature that should manifest via a residual value (
κ
0
/
T
) in the zero-temperature limit. However, this linear in
T
behavior has been reported for very few QSL candidates. Here, we studied the ultralow-temperature thermal conductivity of an effective spin-1/2 triangular QSL candidate Na
2
BaCo(PO
4
)
2
, which has an antiferromagnetic order at very low temperature (
T
N
~ 148 mK), and observed a finite
κ
0
/
T
extrapolated from the data above
T
N
. Moreover, while approaching zero temperature, it exhibits series of quantum spin state transitions with applied field along the
c
axis. These observations indicate that Na
2
BaCo(PO
4
)
2
possibly behaves as a gapless QSL with itinerant spin excitations above
T
N
and its strong quantum spin fluctuations persist below
T
N
.
Although the magnetoelectric effects - the mutual control of electric polarization by magnetic fields and magnetism by electric fields, have been intensively studied in a large number of inorganic ...compounds and heterostructures, they have been rarely observed in organic materials. Here we demonstrate magnetoelectric coupling in a metal-organic framework (CH3)2NH2Mn(HCOO)3 which exhibits an order-disorder type of ferroelectricity below 185 K. The magnetic susceptibility starts to deviate from the Curie-Weiss law at the paraelectric-ferroelectric transition temperature, suggesting an enhancement of short-range magnetic correlation in the ferroelectric state. Electron spin resonance study further confirms that the magnetic state indeed changes following the ferroelectric phase transition. Inversely, the ferroelectric polarization can be improved by applying high magnetic fields. We interpret the magnetoelectric coupling in the paramagnetic state in the metal-organic framework as a consequence of the magnetoelastic effect that modifies both the superexchange interaction and the hydrogen bonding.
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.
The processes X(3872) ... , and γD+D− are searched for in a 9.0 fb−1 data sample collected at center-of-mass energies between 4.178 and 4.278 GeV with the BESIII detector. We observe X(3872) ... . ...and find evidence for X (3872)→γJ/ψ with statistical significances of 7.4 σ and 3.5σ, respectively. No evident signals for X(3872)→γψ(2S) and γD+D− are found, and the upper limit on the relative branching ratio Rγψ ≡ {BX(3872)→γψ(2S)}/{BX(3872)→γJ/ψ} <0.59 is set at 90% confidence level. Measurements of branching ratios relative to decay X(3872)→π+π−J/ψ are also reported for decays ... .,γψ(2S), γJ/ψ, and γD+D−, as well as the non-... three-body decays ... .(ProQuest: ... denotes formulae omitted.)
The exclusive process e+e−→ΛΛ¯, with Λ→pπ− and Λ¯→p¯π+, has been studied at s=2.396 GeV for measurement of the timelike Λ electric and magnetic form factors, GE and GM. A data sample, corresponding ...to an integrated luminosity of 66.9 pb−1, was collected with the BESIII detector for this purpose. A multidimensional analysis with a complete decomposition of the spin structure of the reaction enables a determination of the modulus of the ratio R=|GE/GM| and, for the first time for any baryon, the relative phase ΔΦ=ΦE−ΦM. The resulting values are R=0.96±0.14(stat)±0.02(syst) and ΔΦ=37°±12°(stat)±6°(syst), respectively. These are obtained using the recently established and most precise value of the asymmetry parameter αΛ=0.750±0.010 measured by BESIII. In addition, the cross section is measured with unprecedented precision to be σ=118.7±5.3(stat)±5.1(syst) pb, which corresponds to an effective form factor of |G|=0.123±0.003(stat)±0.003(syst). The contribution from two-photon exchange is found to be negligible. Our result enables the first complete determination of baryon timelike electromagnetic form factors.
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