Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) ...entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.
The aim of this study was to develop a widely accepted prognostic nomogram for extranodal NK/T-cell lymphoma, nasal-type (NKTCL). The clinical data from 1383 patients with NKTCL treated at 10 ...participating institutions between 2000 and 2011 were reviewed. A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. To contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort: stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range, 0.56-0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts. The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL.
Summary
We investigated the secular trends of the incidence and hospitalization cost of hip fracture in Tangshan, China. The incidence of hip fracture and the hospitalization cost were both ...increasing during the observation period.
Introduction
The present study aimed to determine sex-, age-, and fracture type-specific incidence and annual changes in hip fractures in Tangshan, China, between 2007 and 2018.
Methods
We analyzed annual hip fracture incidence using urban hospital data during 2007–2018 and calculated incidence rate/100,000 person years in each age group and sex. We assessed annual changes in incidence among people aged >60 years using linear-by-linear association tests and evaluated hospitalization costs with the Kruskal–Wallis test.
Results
During the study period, we observed an increasing proportion of hip fractures in people >60 years old from 14.2 to 22.79%. Crude hip fracture incidence increased markedly from 140.87 to 306.56/100,000 in women (
p
< 0.01) and from 124.83 to 167.19/100,000 in men (
p
< 0.01) in the age group >60 years. Type-specific analysis indicated significantly increased trends in incidence of cervical and trochanteric fractures among women and cervical fracture among men (
p
< 0.01). In people aged 36–60 years, the trend of hip fracture increased significantly in both sexes. The total and cervical-to-trochanteric ratio in men increased, with significant upward trends (
p
< 0.01). The proportion of cervical fracture was higher than that for trochanteric fracture in women, with stable levels from 2007 to 2018. Hospitalization costs for cervical and trochanteric fractures increased by 51.91% and 53.20%, respectively, during 2011–2018.
Conclusion
Tangshan will have an increasing burden on health care resources attributable to a considerable rise in hip fracture incidence and the older population. Further investigation of risk factors and subsequent implementation of effective measures to prevent hip fracture are needed.
Context.
The astrometric satellite
Gaia
is expected to significantly increase our knowledge as to the properties of the Milky Way. The
Gaia
Early Data Release 3 (EDR3) provides the most precise ...parallaxes for many OB stars, which can be used to delineate the Galactic spiral structure.
Aims.
We investigate the local spiral structure with the largest sample of spectroscopically confirmed young OB stars available to date, and we compare it with what was traced by the parallax measurements of masers.
Methods.
A sample consisting of three different groups of massive young stars, including O–B2 stars, O–B0 stars and O-type stars with parallax accuracies better than 10% was compiled and used in our analysis.
Results.
The local spiral structures in all four Galactic quadrants within ≈5 kpc of the Sun are clearly delineated in detail. The revealed Galactic spiral pattern outlines a clear sketch of nearby spiral arms, especially in the third and fourth quadrants where the maser parallax data are still absent. These O-type stars densify and extend the spiral structure constructed by using the Very Long Baseline Interferometry maser data alone. The clumped distribution of O-type stars also indicates that the Galaxy spiral structure is inhomogeneous.
In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
This study investigates the differences in the microstructure, defects and mechanical behavior of porous structures from a β-type Ti24Nb4Zr8Sn manufactured by electron beam melting (EBM) and ...selective laser melting (SLM). The phases, size and shape of melt pool, volume and distribution of defects are analyzed and correlated to the compressive mechanical and fatigue properties. Due to different powder bed temperatures, the microstructure of EBM and SLM samples consists of α+β phases and a single β phase, respectively. The faster cooling rate during SLM promotes the formation of fine β dendrites, which leads to a higher compressive strength (50 ± 0.9 MPa) and lower Young's Modulus (0.95 ± 0.05 GPa) in comparison to the EBM parts (45 ± 1.1 MPa and 1.34 ± 0.04 GPa respectively). The large defects present within solid strut are likely a result of tin vaporization. The tin vapor is more easily trapped during the SLM process due to a smaller laser spot size and a faster cooling rate. This results in a 10 times increase in the number of defects. These defects have a limited influence on both the static properties and low stresses level fatigue strength, but it causes a reduced and variable fatigue life at high stresses level.
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Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
Context. Solar active region (AR) 12673 in 2017 September produced the two largest flares in Solar Cycle 24: the X9.3 flare on September 6 and the X8.2 flare on September 10. Aims. We attempt to ...investigate the evolutions of the two large flares and their associated complex magnetic system in detail. Methods. Combining observations from the Solar Dynamics Observatory and results of nonlinear force-free field (NLFFF) modeling, we identify various magnetic structures in the AR core region and examine the evolution of these structures during the flares. Results. Aided by the NLFFF modeling, we identify a double-decker flux rope configuration above the polarity inversion line (PIL) in the AR core region. The north ends of these two flux ropes were rooted in a negative- polarity magnetic patch, which began to move along the PIL and rotate anticlockwise before the X9.3 flare on September 6. The strong shearing motion and rotation contributed to the destabilization of the two magnetic flux ropes, of which the upper one subsequently erupted upward due to the kink-instability. Then another two sets of twisted loop bundles beside these ropes were disturbed and successively erupted within five minutes like a chain reaction. Similarly, multiple ejecta components were detected as consecutively erupting during the X8.2 flare occurring in the same AR on September 10. We examine the evolution of the AR magnetic fields from September 3 to 6 and find that five dipoles emerged successively at the east of the main sunspot. The interactions between these dipoles took place continuously, accompanied by magnetic flux cancellations and strong shearing motions. Conclusions. In AR 12673, significant flux emergence and successive interactions between the different emerging dipoles resulted in a complex magnetic system, accompanied by the formations of multiple flux ropes and twisted loop bundles. We propose that the eruptions of a multi-flux-rope system resulted in the two largest flares in Solar Cycle 24.
AMPK has emerged as a critical mechanism for salutary effects of polyphenols on lipid metabolic disorders in type 1 and type 2 diabetes. Here we demonstrate that AMPK interacts with and directly ...phosphorylates sterol regulatory element binding proteins (SREBP-1c and -2). Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin. AMPK stimulates Ser372 phosphorylation, suppresses SREBP-1c cleavage and nuclear translocation, and represses SREBP-1c target gene expression in hepatocytes exposed to high glucose, leading to reduced lipogenesis and lipid accumulation. Hepatic activation of AMPK by the synthetic polyphenol S17834 protects against hepatic steatosis, hyperlipidemia, and accelerated atherosclerosis in diet-induced insulin-resistant LDL receptor-deficient mice in part through phosphorylation of SREBP-1c Ser372 and suppression of SREBP-1c- and -2-dependent lipogenesis. AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis.
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▴ AMPKα subunit interacts with and directly phosphorylates SREBP-1c and SREBP-2 ▴ Phosphorylation of SREBP-1c by AMPK represses de novo lipogenesis in hepatocytes ▴ AMPK inhibits SREBP cleavage and gene transcription in insulin-resistant mice ▴ SREBP suppression by polyphenols attenuates hepatic steatosis and atherosclerosis
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