Aims/hypothesis
FTO
harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for
FTO
in obesity risk in Asians, its association with type 2 ...diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the
FTO
locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
Methods
All studies published on the association between
FTO
-rs9939609 (or proxy
r
2
> 0.98) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
Results
The
FTO
-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (
p
= 9.0 × 10
−19
), overweight by 1.13-fold/allele (
p
= 1.0 × 10
−11
) and type 2 diabetes by 1.15-fold/allele (
p
= 5.5 × 10
−8
). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele,
p
= 6.6 × 10
−5
). The
FTO
-rs9939609 minor allele increased BMI by 0.26 kg/m
2
per allele (
p
= 2.8 × 10
−17
), WHR by 0.003/allele (
p
= 1.2 × 10
−6
), and body fat percentage by 0.31%/allele (
p
= 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of
FTO
variation on obesity-related traits and type 2 diabetes was similar in the two populations.
Conclusions/interpretation
FTO
is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore,
FTO
is also associated with type 2 diabetes independently of BMI.
Summary
Background
Keloid and hypertrophic scar (HS) are two pathological forms of excessive dermal fibrosis, which are due to aberrant wound‐healing responses. Accumulating evidence suggests that ...aberrant activity of growth factors and increased numbers of growth factor receptors play an important role in the formation of pathological scar.
Aim
We examined the expression level of insulin‐like growth factor‐1 receptor (IGF‐IR) in keloid, HS and normal skin.
Methods
IGF‐IR expression was analyzed by immunohistochemistry, real‐time PCR and western blotting on tissues and fibroblasts from 30 patients, comprising 10 patients with keloid and 20 with HS (10 with immature and 10 with mature HS), and from 10 age‐matched and sex‐matched healthy controls.
Results
Immunoreactivity to IGF‐IR was found in dermal fibroblasts of keloid (90%), immature HS, (80%) and mature HS (30%), but not in normal skin. There was no statistically significant difference in immunoreactivity scores between keloid and immature HS, but there was a significant difference (P < 0.01) between mature and immature HS. Real‐time PCR and western blot analysis confirmed that there was high expression of IGF‐IR in keloid and immature HS fibroblasts, but not in mature HS or normal skin fibroblasts. IGF‐IR was expressed in the overlying epidermis, and there was no significant difference between the groups.
Conclusions
IGF‐IR may be involved in the pathogenesis of keloid and HS. Given that IGF‐IR are predominantly expressed on dermal fibroblasts, targeting of IGF‐IR in fibroblasts may be of benefit to prevent scarring.
Sialic acid‐binding immunoglobulin‐like lectin‐7 (Siglec‐7) is an inhibitory receptor expressed on natural killer (NK) cells. In this study, we investigated the relationship between Siglec‐7 ...expression and NK cell functions. Siglec‐7 was highly expressed on NK cells and was preferentially expressed by mature NK cells from peripheral blood of healthy adults. Siglec‐7+ NK cells displayed higher levels of activating receptors CD38, CD16, DNAM1, NKp30 and NKp46, but lower levels of inhibitory receptors such as NKG2A and CD158b, compared with Siglec‐7– NK cells. Functional tests showed that Siglec‐7+ NK cells displayed more CD107a degranulation and IFN‐γ production than Siglec‐7– NK cells. Siglec‐7 inhibited NK cell functions when interacting with specific antibodies. These data suggest that Siglec‐7 defines a highly functional NK cell subset and suppresses NK cell‐mediated functions when cross‐linked with specific antibodies.
In order to determine the orbital characters on the various Fermi surface pockets of the Fe-based superconductors Ba sub(0.6)K sub(0.4)Fe sub(2)As sub(2) and FeSe sub(0.45)Te sub(0.55), we introduce ...a method to calculate photoemission matrix elements. We compare our simulations to experimental data obtained with various experimental configurations of beam orientation and light polarization. We show that the photoemission intensity patterns revealed from angle-resolved photoemission spectroscopy measurements of Fermi surface mappings and energy-momentum plots along high-symmetry lines exhibit asymmetries carrying precious information on the nature of the states probed, information that is destroyed after the data symmetrization process often performed in the analysis of angle-resolved photoemission spectroscopy data. Our simulations are consistent with Fermi surfaces originating mainly from the dxy, dxz, and dyyz orbitals in these materials.
•Ultrasound promotes α(Cu) nucleation rate by three orders of magnitude.•Ultrasound transforms α(Cu) growing orientation from preferred (111) plane to isotropy.•Ultrasound enhances the yield strength ...of Cu-7%Al-4%Ni-2.5%Mn alloy by three times.•Dislocation and grain strengthening are mechanisms of the alloy reinforcement.
An intensive field of 20 kHz power ultrasound with various amplitudes was applied during the solidification process of quaternary Cu-7%Al-4%Ni-2.5%Mn single-phase alloy to investigate its dynamic solidification mechanism and mechanical performance improvement. It is found that α(Cu) phase nucleates at small undercoolings and mainly grows along (111) crystalline plane direction into coarse dendrites with developed secondary arms. With the rise of amplitude, ultrasonic wave increases the nucleation rate by improving the wetting effect between alloy melt and impurities and also breaks some growing dendrites into fragments. Once the ultrasonic amplitude reaches the maximum of 15.2 µm, the prominent cavitation effect further increases the nucleation rate by three orders of magnitude, and also leads to the symmetrical distribution of temperature field, solute field and flow field in the solidification front, eventually resulting in the formation of tiny equiaxed α(Cu) grains without any obvious preferred growth orientation, inside which the solute distribution also tends to become uniform. Meanwhile, the compressive yield strength of Cu-7%Al-4%Ni-2.5%Mn alloy is significantly increased by 3 times after ultrasonic solidification. Theoretical analysis indicates that grain strengthening and dislocation strengthening are the two main reinforcement factors induced by power ultrasound.
Cellulose is the most abundant biopolymer on Earth, found in trees, waste from agricultural crops and other biomass. The fibres that comprise cellulose can be broken down into building blocks, known ...as fibrillated cellulose, of varying, controllable dimensions that extend to the nanoscale. Fibrillated cellulose is harvested from renewable resources, so its sustainability potential combined with its other functional properties (mechanical, optical, thermal and fluidic, for example) gives this nanomaterial unique technological appeal. Here we explore the use of fibrillated cellulose in the fabrication of materials ranging from composites and macrofibres, to thin films, porous membranes and gels. We discuss research directions for the practical exploitation of these structures and the remaining challenges to overcome before fibrillated cellulose materials can reach their full potential. Finally, we highlight some key issues towards successful manufacturing scale-up of this family of materials.
Abstract
A sub-array of the Large High Altitude Air Shower Observatory (LHAASO), KM2A is mainly designed to observe a large fraction of the northern sky to hunt for γ-ray sources at energies above 10 ...TeV. Even though the detector construction is still underway, half of the KM2A array has been operating stably since the end of 2019. In this paper, we present the KM2A data analysis pipeline and the first observation of the Crab Nebula, a standard candle in very high energy γ-ray astronomy. We detect γ-ray signals from the Crab Nebula in both energy ranges of 10
100 TeV and
100 TeV with high significance, by analyzing the KM2A data of 136 live days between December 2019 and May 2020. With the observations, we test the detector performance, including angular resolution, pointing accuracy and cosmic-ray background rejection power. The energy spectrum of the Crab Nebula in the energy range 10-250 TeV fits well with a single power-law function d
N
/d
E
= (1.13
0.05
0.08
)
10
(
E
/20 TeV)
cm
s
TeV
. It is consistent with previous measurements by other experiments. This opens a new window of γ-ray astronomy above 0.1 PeV through which new ultrahigh-energy γ-ray phenomena, such as cosmic PeVatrons, might be discovered.
Polycomb group (PcG) proteins play an important role in development and stem cell maintenance, and their dysregulation have been closely linked to oncogenesis and cancer stem cell phenotypes. Here, ...we found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts. In contrast, glioma cells overexpressing NSPc1 exhibited a stem cell-like phenotype, up-regulated expression of stemness markers NESTIN, CD133 and SOX2, and an enhanced capacity to propagate subcutaneous xenografts. Furthermore, we identified that NSPc1 epigenetically repressed the expression of retinol dehydrogenase 16 (RDH16) by directly binding to a region upstream (-1073 to -823) of the RDH16 promoter. Next, we confirmed that RDH16 is a stemness suppressor that partially rescues SLCs from the NSPc1-induced increase in neurosphere formation. Finally, we showed that ATRA partly reversed the NSPc1-induced stemness enhancement in SLCs, through mechanisms correlated with an ATRA-dependent decrease in the expression of NSPc1. Thus, our results demonstrate that NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of ATRA via targeting RDH16 and may provide novel targets for glioma treatment in the future.
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.
The cross section of the process e+e−→K+K− is measured at a number of center-of-mass energies s from 2.00 to 3.08 GeV with the BESIII detector at the Beijing Electron Positron Collider (BEPCII). The ...results provide the best precision achieved so far. A resonant structure around 2.2 GeV is observed in the cross section line shape. A Breit-Wigner fit yields a mass of M=2239.2±7.1±11.3 MeV/c2 and a width of Γ=139.8±12.3±20.6 MeV, where the first uncertainties are statistical and the second ones are systematic. In addition, the timelike electromagnetic form factor of the kaon is determined at the individual center-of-mass energy points.
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