MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular ...carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.
Understanding how flowering phenology responds to warming and cooling (i.e., symmetric or asymmetric response) is needed to predict the response of flowering phenology to future climate change that ...will happen with the occurrence of warm and cold years superimposed upon a long-term trend. A three-year reciprocal translocation experiment was performed along an elevation gradient from 3200 m to 3800 m in the Tibetan Plateau for six alpine plants. Transplanting to lower elevation (warming) advanced the first flowering date (FFD) and transplanting to higher elevation (cooling) had the opposite effect. The FFD of early spring flowering plants (ESF) was four times less sensitive to warming than to cooling (by −2.1 d/°C and 8.4 d/°C, respectively), while midsummer flowering plants (MSF) were about twice as sensitive to warming than to cooling (−8.0 d/°C and 4.9 d/°C, respectively). Compared with pooled warming and cooling data, warming alone significantly underpredicted 3.1 d/°C for ESF and overestimated 1.7 d/°C for MSF. These results suggest that future empirical and experimental studies should consider nonlinear temperature responses that can cause such warming-cooling asymmetries as well as differing life strategies (ESF vs. MSF) among plant species.
Objectives
Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive ...polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study.
Design
A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020.
Setting and Participants
The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach.
Methods
Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models.
Results
Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The “depression with cognitive impairment” group (EPP: aOR=4.35, 95% CI 3.52–5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46–3.02, p<0.01) and the “impairment in all domains” group (EPP: aOR=9.02, 95% CI 7.16–11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24–4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment.
Conclusions
We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the “depression with cognitive impairment” and “impairment in all domains”, was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.
Abstract We report the timing analysis of PSR J1846−0513, a pulsar discovered by the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in Commensal Radio Astronomy FAST Survey. The pulsar ...possesses a spin period of 23.36 ms and a spin-down rate ( P ̇ ) of 1.0106(3) × 10 −18 s s −1 , and it is located in an eccentric orbit ( e ∼0.208) with an orbital period of 0.61 days. The characteristic age and surface magnetic field of the pulsar are found to be 366.62 Myr and 4.9178 × 10 9 G, respectively, indicating that it is a recycled pulsar. Using over two years of timing data, we measure the periastron advance ω ̇ = 0.8956(8) deg yr −1 . By assuming that this effect is purely relativistic, we have estimated the total mass M = 2.6287(35) M ⊙ and obtained an upper limit for the pulsar mass and a lower limit for the companion’s mass. Our results indicate that this is a double neutron star system.
Abstract
We searched for shocked carbon chain chemistry (SCCC) sources with C
3
S abundances surpassing those of HC
5
N toward the dark cloud L1251, using the Effelsberg telescope at the
K
band ...(18–26 GHz). L1251-1 and L1251-3 are identified as the most promising SCCC sources. The two sources harbor young stellar objects. We conducted mapping observations toward L1251-A, the western tail of L1251, at
λ
∼ 3 mm with the Purple Mountain Observatory 13.7 m and the Nobeyama Radio Observatory 45 m telescopes in lines of C
2
H, N
2
H
+
, CS, HCO
+
, SO, HC
3
N, and C
18
O as well as in CO 3–2 using the James Clerk Maxwell Telescope (JCMT). The spectral data were combined with archival data including Spitzer and Herschel continuum maps for further analysis. Filamentary substructures labeled as F1–F6 were extracted in L1251, with F1 being associated with L1251-A hosting L1251-1. The peak positions of dense gas traced by HCO
+
are misaligned relative to those of the dust clumps. Episodic outflows are common in this region. The twisted morphology of F1 and velocity distribution along L1251-A may originate from stellar feedback. SCCC in L1251-1 may have been caused by outflow activities originated from the infrared source IRS1. The signposts of ongoing SCCC and the broadened line widths of C
3
S and C
4
H in L1251-1 as well as the distribution of HC
3
N are also related to outflow activities in this region. L1251-1 (IRS1) together with the previously identified SCCC source IRS3 demonstrate that L1251-A is an excellent region to study SCCC.
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
Nanocomposites based on poly (phenylene sulfide) (PPS) and expanded graphite (EG) or ultrasonicated EG (S-EG) were prepared by melt blending. Morphologies of the nanocomposites were examined using ...both SEM and TEM. Electrical conductivity and thermal stability of PPS were notably enhanced by the introduction of EG. The percolation threshold values are 1
wt% (S-EG) and 2
wt% (EG) for PPS/S-EG and PPS/EG nanocomposites, respectively. The variation of mechanical strength with the weight fraction of EG and S-EG in the nanocomposites showed somewhat correlation with the threshold filler concentration. The crystallization behavior of PPS matrix in the nanocomposites was investigated using DSC, and the results indicated that the crystallization process was significantly accelerated, leading to an increase in crystallinity.
The effect of tunnel slope on the fire induced hot gas temperature profile beneath the ceiling has not been clarified nor included in existing models. Thus, in this paper experiments are carried out ...in a reduced scale model tunnel with dimensions of 6 m (length) × 1.3 m (width) × 0.8 m (height), which is positioned within a 72 m long wind tunnel. The slopes of the model tunnel are varied at three typical different degrees, 0%, 3% and 5%. A LPG porous gas burner is used as fire source. Both the maximum gas temperature and the temperature distribution along the tunnel ceiling are measured and compared with previous models. Results show that those models overestimates the maximum temperature beneath the ceiling of a slopping tunnel fire. The gas temperature decays faster along the ceiling for tunnels with higher slope. Empirical correlations are then proposed to modify the current models to include the tunnel slope factor. The predictions by the modified equations of this work agree well with the measured data in both the maximum temperature and temperature decay beneath the ceiling of the tunnel with different slopes.
► Experiments are carried out in a reduced scale model tunnel. ► Gas temperature data beneath the ceiling in a slopping tunnel fire is obtained. ► Tunnel slope factor is included into the current equations. ► Modified equations agree well with the measured data.
Stem cells were characterized by their stemness: self-renewal and pluripotency. Mesenchymal stem cells (MSCs) are a unique type of adult stem cells that have been proven to be involved in tissue ...repair, immunoloregulation and tumorigenesis. Irradiation is a well-known factor that leads to functional obstacle in stem cells. However, the mechanism of stemness maintenance in human MSCs exposed to irradiation remains unknown. We demonstrated that irradiation could induce reactive oxygen species (ROS) accumulation that resulted in DNA damage and stemness injury in MSCs. Autophagy induced by starvation or rapamycin can reduce ROS accumulation-associated DNA damage and maintain stemness in MSCs. Further, inhibition of autophagy leads to augment of ROS accumulation and DNA damage, which results in the loss of stemness in MSCs. Our results indicate that autophagy may have an important role in protecting stemness of MSCs from irradiation injury.
Abstract
PSR J2150+3427 is a 0.654 s pulsar discovered by the Commensal Radio Astronomy FAST Survey. From the follow-up observations, we find that the pulsar is in a highly eccentric orbit (
e
= ...0.601) with an orbital period of 10.592 days and a projected semimajor axis of 25.488 lt-s. Using 2.7 yr of timing data, we also measured the rate of periastron advance
ω
̇
= 0.0115(4) deg yr
−1
. An estimate for the total mass of the system using the
ω
̇
gives
M
tot
= 2.59(13)
M
⊙
, which is consistent with most of the known double neutron star (DNS) systems and one neutron star (NS)–white dwarf (WD) system named B2303+46. Combining
ω
̇
with the mass function of the system gives the masses of
M
p
< 1.67 and
M
c
> 0.98
M
⊙
for the pulsar and the companion star, respectively. This constraint, along with the spin period and orbital parameters, suggests that it is possibly a DNS system, and we cannot entirely rule out the possibility of an NS–WD system. Future timing observations will vastly improve the uncertainty in
ω
̇
, and are likely to allow the detection of additional relativistic effects, which can be used to modify the values of
M
p
and
M
c
. With a spin-down luminosity of
E
̇
= 5.07(6) × 10
29
erg s
−1
, PSR J2150+3427 is a very low-luminosity pulsar, with only the binary pulsar J2208+4610 having a smaller
E
̇
.
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