Although the skeleton is one of the predominant sites for breast cancer metastasis, why breast cancer cells often become dormant after homing to bone is not well understood. Here, we reported an ...intrinsic self-defense mechanism of bone cells against breast cancer cells: a critical role of connexin (Cx) 43 hemichannels in osteocytes in the suppression of breast cancer bone metastasis. Cx43 hemichannels allow passage of small molecules between the intracellular and extracellular environments. The treatment of bisphosphonate drugs, either alendronate (ALN) or zoledronic acid (ZOL), opened Cx43 hemichannels in osteocytes. Conditioned media (CM) collected from MLO-Y4 osteocyte cells treated with bisphosphonates inhibited the anchorage-independent growth, migration and invasion of MDA-MB-231 human breast cancer cells and Py8119 mouse mammary carcinoma cells, and this inhibitory effect was attenuated with Cx43(E2), a specific hemichannel-blocking antibody. The opening of osteocytic Cx43 hemichannels by mechanical stimulation had similar inhibitory effects on breast cancer cells and this inhibition was attenuated by Cx43(E2) antibody as well. These inhibitory effects on cancer cells were mediated by ATP released from osteocyte Cx43 hemichannels. Furthermore, both Cx43 osteocyte-specific knockout mice and osteocyte-specific Δ130-136 transgenic mice with impaired Cx43 gap junctions and hemichannels showed significantly increased tumor growth and attenuated the inhibitory effect of ZOL. However, R76W transgenic mice with functional hemichannels but not gap junctions in osteocytes did not display a significant difference. Together, our studies establish the specific inhibitory role of osteocytic Cx43 hemichannels, and exploiting the activity of this channel could serve as a de novo therapeutic strategy.
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.
The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This ...work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2
/
years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.
Graphene nanosheets (GNs) were synthesized and used as a substitute for platinum as counter-electrode materials for dye-sensitized solar cells (DSSCs). The as-synthesized GNs were dispersed in a ...mixture of terpineol and ethyl cellulose. GN films were screen-printed on fluorine-doped tin oxide (FTO) slides using the formed GN dispersions. GN counter-electrodes were produced by annealing the GN films at different temperatures. The annealed GN films revealed an unusual 3D network structure. Structural and electrochemical properties of the formed GN counter-electrodes were examined by field emission scanning electron microscopy, Raman spectroscopy and electrochemical impedance spectroscopy. It was found that the annealing temperature of GN materials played an important role in the quality of the GN counter-electrode and the photovoltaic performance of the resultant DSSC. The grown DSSCs with graphene-based counter-electrodes exhibited a conversion efficiency high up to 6.81%.
The ground state of the simple Heisenberg nearest-neighbor quantum kagome antiferromagnetic model is a magnetically disordered spin liquid, yet various perturbations may lead to fundamentally ...different states. Here we disclose the origin of magnetic ordering in the structurally perfect kagome material YCu3(OH)6Cl3 , which is free of the widespread impurity problem. Ab initio calculations and modeling of its magnetic susceptibility reveal that, similar to the archetypal case of herbertsmithite, the nearest-neighbor exchange is by far the dominant isotropic interaction. Dzyaloshinskii-Moriya (DM) anisotropy deduced from electron spin resonance, susceptibility, and specific-heat data is, however, significantly larger than in herbertsmithite. By enhancing spin correlations within kagome planes, this anisotropy is essential for magnetic ordering. Our study isolates the effect of DM anisotropy from other perturbations and unambiguously confirms the predicted phase diagram.
To conduct a large population-based survey on multiple sclerosis (MS) prevalence in Shanghai, China.
We established a network of physicians, mainly neurologists, for identifying prevalent patients ...with MS and systematically checked inpatient registers at each hospital in the study area for patients with a diagnosis of MS, neuromyelitis optica, or other demyelinating disorders. MS diagnosis in patients was validated by senior neurologists according to the McDonald criteria.
In total, 123 patients with a validated MS diagnosis from the study population, 8.86 million inhabitants with permanent residence in Shanghai, were alive on the prevalence day. The crude MS prevalence rate was 1.39 cases per 100,000 inhabitants (95% CI: 1.16 to 1.66 cases) in the study population in Shanghai. There were 79 female and 44 male patients with MS, a female-to-male ratio of 1.8. Nearly all (96%) of the patients with validated MS had been examined by MRI.
Multiple sclerosis prevalence in Shanghai is in line with that reported for other Asian populations.
In high-Tc superconductors the magnetic and electronic properties are determined by the probability that valence electrons jump virtually from site to site in the CuO2 planes, a mechanism opposed by ...on-site Coulomb repulsion and favoured by hopping integrals. The spatial extent of the latter is related to transport properties, including superconductivity, and to the dispersion relation of spin excitations (magnons). Here, for three antiferromagnetic parent compounds (single-layer Bi2 Sr0.9 La1.1 CuO6+δ , double-layer Nd1.2 Ba1.8 Cu3 O6 and infinite-layer CaCuO2 ) differing by the number of apical atoms, we compare the magnetic spectra measured by resonant inelastic X-ray scattering over a significant portion of the reciprocal space and with unprecedented accuracy. We observe that the absence of apical oxygens increases the in-plane hopping range and, in CaCuO2 , it leads to a genuine three-dimensional (3D) exchange-bond network. These results establish a corresponding relation between the exchange interactions and the crystal structure, and provide fresh insight into the materials dependence of the superconducting transition temperature.
Objectives
We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese.
Methods
The telomere restriction fragment (TRF) length of leukocytes in ...the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed.
Results
Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function.
Conclusion
The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.
In the northern hemisphere, there are six permanent or semi-permanent atmospheric activity centers, namely the Icelandic Low, Aleutian Low, India Low, Mongolia High, North Pacific High, and North ...Atlantic High. The first four are semi-permanent action centers and the last two are permanent circulation systems. The India Low exists only during the summer. By using 160 years (1850–2009) of monthly mean sea level pressure data from the Hadley Centre in the UK, we conduct a comprehensive study of the five boreal winter atmospheric centers of action (ACAs). Based on a unified definition and a method determined in previous studies, we calculate the indices of areal coverage (S), intensity (P), and position of action center (
λ
c
,
φ
c
) for each of these five ACAs. Through an in-depth analysis of these indices and their relationships with climate variables, we evaluate the indices by describing and explaining areal climate anomalies, particularly precipitation and temperature anomalies in China. We show that (1) ACAs significantly influence the climate anomalies of surrounding areas (2) the influences of oceanic ACAs are larger and the intensity anomalies of ACAs have a greater impact than their location displacement, and (3) ACAs exert more control on temperature than they do on precipitation. For the two ACAs over the north Atlantic, the impacts of their intensities on the anomalies of temperature and precipitation are similar. For the two ACAs over the north Pacific, their influences are almost the opposite. The most influential ACA for climate anomalies in China during the boreal winter is HMO. When HMO is stronger, China has a colder winter and it is wetter in the north. With stronger ACAs in the upstream, i.e., the Icelandic Low and North Atlantic High, northern China has a warmer winter. The ACAs over the north Pacific exert little influence on climate anomalies in China during winter. The analyses presented in this paper provide a set of useful indices for defining and describing ACAs, and they suggest insightful applications for these indices.
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