Cancer-associated fibroblasts (CAFs) activated by tumour cells are the predominant type of stromal cells in breast cancer tissue. The reciprocal effect of CAFs on breast cancer cells and the ...underlying molecular mechanisms are not fully characterised.
Stromal fibroblasts were isolated from invasive breast cancer tissues and the conditioned medium of cultured CAFs (CAF-CM) was collected to culture the breast cancer cell lines MCF-7, T47D and MDA-MB-231. Neutralising antibody and small-molecule inhibitor were used to block the transforming growth factor-β (TGF-β) signalling derived from CAF-CM, which effect on breast cancer cells.
The stromal fibroblasts isolated from breast cancer tissues showed CAF characteristics with high expression levels of α-smooth muscle actin and SDF1/CXCL12. The CAF-CM transformed breast cancer cell lines into more aggressive phenotypes, including enhanced cell-extracellular matrix adhesion, migration and invasion, and promoted epithelial-mesenchymal transition (EMT). Cancer-associated fibroblasts secreted more TGF-β1 than TGF-β2 and TGF-β3, and activated the TGF-β/Smad signalling pathway in breast cancer cells. The EMT phenotype of breast cancer cells induced by CAF-CM was reversed by blocking TGF-β1 signalling.
Cancer-associated fibroblasts promoted aggressive phenotypes of breast cancer cells through EMT induced by paracrine TGF-β1. This might be a common mechanism for acquiring metastatic potential in breast cancer cells with different biological characteristics.
Summary
Breeding for good meat quality performance while maintaining large body size and desirable carcass traits has been the major challenge for modern swine selective breeding. To address this ...goal, in the present work we studied five related populations produced by two commercial breeds (Berkshire and Duroc) and two Chinese breeds (Licha black pig and Lulai black pig). A single‐trait GWAS performed on 20 body size and carcass traits using a self‐developed China Chip‐1 porcine SNP50K BeadChip identified 11 genome‐wide significant QTL on nine chromosomes and 22 suggestive QTL on 15 chromosomes. For the 11 genome‐wide significant QTL, eight were detected in at least two populations, and the rest were population‐specific and only mapped in Shanxia black pig. Most of the genome‐wide significant QTL were pleiotropic; for example, the QTL around 75.65 Mb on SSC4 was associated with four traits at genome‐wide significance level. After screening the genes within 50 kb of the top SNP for each genome‐wide significant QTL, NR6A1 and VRTN were chosen as candidate genes for vertebrae number; PLAG1 and BMP2 were identified as candidate genes for body size; and MC4R was the strong candidate gene for body weight. The four genes have been reported as candidates for thoracic vertebrae number, lumbar vertebrae number, carcass length and body weight respectively in previous studies. The effects of VRTN on thoracic vertebrae number, carcass length and body length have been verified in Shanxia black pig. Therefore, the VRTN genotype could be used in gene‐assisted selection, and this could accelerate genetic improvement of body size and carcass traits in Shanxia black pig.
Abstract
The fast transitions between different types of quasi-periodic oscillations (QPOs) are generally observed in black hole transient sources (BHTs). We present a detailed study of the timing ...and spectral properties of the transitions of type-B QPOs in MAXI J1348–630, observed by Insight-HXMT. The fractional rms variability–energy relationship and energy spectra reveal that type-B QPOs probably originate from jet precession. Compared to a weak power-law dominated power spectrum, when type-B QPOs are present, the corresponding energy spectrum shows an increase in the Comptonization component and the need for the
xillverCp
component, and a slight increase in the height of the corona when using the
relxilllp
model. Therefore, we suggest that a coupled inner disk-jet region is responsible for the observed type-B QPO transitions. The timescale for the appearance/disappearance of type-B QPOs is either long or short (seconds), which may indicate instability of the disk-jet structure. For these phenomena, we hypothesize that the Bardeen–Petterson effect causes the disk-jet structure to align with the BH spin axis or that the disappearance of small-scale jets bound by the magnetic flux tubes leads to the disappearance of type-B QPOs. We observed three events regarding the B/C transitions, one of which occurred over a short time period from ∼9.2 Hz (C) to ∼4.8 Hz (B). The energy spectral analysis for the other two transitions shows that when type-C QPO is present, the Comptonization flux is higher, the spectrum is harder, and the inner radius of the disk changes insignificantly. We suggest that type-C QPOs probably originate from relatively stronger jets or the corona.
AbstractThis study estimated the wind gust factor and turbulence intensity for hurricane winds that are modeled as a nonstationary non-Gaussian process. The estimation considered the time-varying ...mean wind velocity, and the time–frequency decomposition using S-transform characterized the time-varying amplitude and frequency content of the fluctuating wind. Winds simulated by applying a newly developed algorithm were used to augment the sample size. Results indicate that the standardized power spectral density function of hurricane winds can be represented in terms of the reduced frequency but with time-varying mean wind velocity. The standardized fluctuating wind is only weakly non-Gaussian; the average skewness and kurtosis coefficients are not very sensitive to whether the 10-or 60-min time-varying mean wind speed is considered. The assessed relation between the gust factor and turbulence intensity indicates that such a relationship is influenced by whether the instantaneous aspect of the nonstationary process is considered. There is large uncertainty in the developed relationship. By removing samples associated with a low mean wind velocity, the largest value of the estimated gust factor decreases. The consideration of the non-Gaussian aspect of the fluctuating wind to estimate the gust factor could be important as turbulence intensity increases.
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating ...reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.
Boson sampling is a well-defined task that is strongly believed to be intractable for classical computers, but can be efficiently solved by a specific quantum simulator. However, an outstanding ...problem for large-scale experimental boson sampling is the scalability. Here we report an experiment on boson sampling with photon loss, and demonstrate that boson sampling with a few photons lost can increase the sampling rate. Our experiment uses a quantum-dot-micropillar single-photon source demultiplexed into up to seven input ports of a 16×16 mode ultralow-loss photonic circuit, and we detect three-, four- and fivefold coincidence counts. We implement and validate lossy boson sampling with one and two photons lost, and obtain sampling rates of 187, 13.6, and 0.78 kHz for five-, six-, and seven-photon boson sampling with two photons lost, which is 9.4, 13.9, and 18.0 times faster than the standard boson sampling, respectively. Our experiment shows an approach to significantly enhance the sampling rate of multiphoton boson sampling.
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).
Abstract We report the phase-resolved spectral results of the first Galactic pulsating ultraluminous X-ray source (PULX) Swift J0243.6+6124, modeling its 2017–2018 outburst peak using data collected ...by the Hard X-ray Modulation Telescope (Insight-HXMT). The broad energy coverage of Insight-HXMT allows us to obtain a more accurate spectral continuum to reduce the coupling of broad iron line profiles with other components. We use three different continuum spectrum models but obtain similar iron line results. For the first time, we detect the pulse characteristics of the broad iron line in a PULX. The variation in the width and intensity of this iron line with σ ∼ 1.2–1.5 keV has a phase offset of about 0.25 from the pulse phase. We suggest that the uneven irradiation of the thick inner disk by the accretion column produces the modulated variation of the broad iron line. In addition, the nonpulsed narrow line is suggested to come from the outer disk region.
Our current understanding of the cosmic star formation history at
z
> 3 is primarily based on UV-selected galaxies (Lyman-break galaxies, i.e., LBGs). Recent studies of
H
-dropouts (HST-dark ...galaxies) have revealed that we may be missing a large proportion of star formation that is taking place in massive galaxies at
z
> 3. In this work, we extend the
H
-dropout criterion to lower masses to select optically dark or faint galaxies (OFGs) at high redshifts in order to complete the census between LBGs and
H
-dropouts. Our criterion (
H
> 26.5 mag & 4.5 < 25 mag) combined with a de-blending technique is designed to select not only extremely dust-obscured massive galaxies but also normal star-forming galaxies (typically
E
(
B
−
V
) > 0.4) with lower stellar masses at high redshifts. In addition, with this criterion, our sample is not contaminated by massive passive or old galaxies. In total, we identified 27 OFGs at
z
phot
> 3 (with a median of
z
med
= 4.1) in the GOODS-ALMA field, covering a wide distribution of stellar masses with log(
M
⋆
/
M
⊙
) = 9.4 − 11.1 (with a median of log(
M
⋆med
/
M
⊙
) = 10.3). We find that up to 75% of the OFGs with log(
M
⋆
/
M
⊙
) = 9.5 − 10.5 were neglected by previous LBGs and
H
-dropout selection techniques. After performing an optical-to-millimeter stacking analysis of the OFGs, we find that rather than being limited to a rare population of extreme starbursts, these OFGs represent a normal population of dusty star-forming galaxies at
z
> 3. The OFGs exhibit shorter gas depletion timescales, slightly lower gas fractions, and lower dust temperatures than the scaling relation of typical star-forming galaxies. Additionally, the total star formation rate (SFR
tot
= SFR
IR
+ SFR
UV
) of the stacked OFGs is much higher than the SFR
UV
corr
(SFR
UV
corrected for dust extinction), with an average SFR
tot
/SFR
UV
corr
= 8 ± 1, which lies above (∼0.3 dex) the 16–84th percentile range of typical star-forming galaxies at 3 ≤
z
≤ 6. All of the above suggests the presence of hidden dust regions in the OFGs that absorb all UV photons, which cannot be reproduced with dust extinction corrections. The effective radius of the average dust size measured by a circular Gaussian model fit in the
uv
plane is
R
e(1.13 mm)
= 1.01 ± 0.05 kpc. After excluding the five LBGs in the OFG sample, we investigated their contributions to the cosmic star formation rate density (SFRD). We found that the SFRD at
z
> 3 contributed by massive OFGs (log(
M
⋆
/
M
⊙
) > 10.3) is at least two orders of magnitude higher than the one contributed by equivalently massive LBGs. Finally, we calculated the combined contribution of OFGs and LBGs to the cosmic SFRD at
z
= 4 − 5 to be 4 × 10
−2
M
⊙
yr
−1
Mpc
−3
, which is about 0.15 dex (43%) higher than the SFRD derived from UV-selected samples alone at the same redshift. This value could be even larger, as our calculations were performed in a very conservative way.
The objective of this study is to analyse the factors affecting late toxicity for nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).
Seven hundred and ...eighty-nine consecutive NPC patients treated with IMRT at our centre from January 2003 to February 2008 were retrospectively analysed. Radiotherapy-related complications were categorised using the RTOG Late Radiation Morbidity Scoring Criteria and the Common Terminology Criteria for Adverse Events (Version 3.0). Two hundred and thirty-three patients were treated with IMRT alone (group 1) and 556 patients underwent cisplatin-based chemotherapy (group 2).
Median follow-up was 65 months (range, 4-106 months). The 5-year major late toxicity rate was significantly greater in group 2 than group 1 (63.2% vs 42.0%, P<0.001). Multivariate analyses showed that N category, T category and chemotherapy were significant factors. The maximal dose (Dmax) to the temporal lobe was a significant factor affecting temporal lobe injury (TLI), with a hazard ratio of 1.26 (95% confidence interval (CI), 1.18-1.35; P<0.001) per 1-Gy increase. The 5-year TLI rate increased from 0.8% for 284 lobes with Dmax <65.77 Gy to 27.1% for 176 lobes with greater doses (P<0.001). Logistic regression showed that the hazard ratio attributed to the parotid gland mean dose was 1.36 (95% CI, 1.21-1.53; P<0.001) per 1-Gy increase. Chemotherapy was not a significant factor (P=0.211).
With the application of IMRT, the incidence of radiation-related complications has been reduced except for TLI. The significant factors affecting the risk of TLI included T category, chemotherapy and Dmax.
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