Highlights • Gastrodin improves learning and memory abilities of Tg2576 mice. • Gastrodin attenuates intracellular oxidative stress in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 ...expression and PKR/eIF2α pathway in hippocampi of Tg2576 mice. • Gastrodin suppresses BACE1 via inhibiting PKR/eIF2α in SH-SY5Y cells under oxidative stress.
Cells apoptosis induced by intense heat stress is the prominent feature of heat-related illness. However, little is known about the biological effects of heat stress on cells apoptosis. Herein, we ...presented evidence that intense heat stress could induce early apoptosis of HUVEC cells through activating mitochondrial pathway with changes in mitochondrial membrane potential(ΔΨm), release of cytochrome c, and activation of caspase-9 and -3. We further revealed that p53 played a crucial role in heat stress-induced early apoptosis, with p53 protein rapidly translocated into mitochondria. Using pifithrin-α(PFT), a p53's mitochondrial translocation inhibitor, we found that pretreated with PFT, heat stress induced mitochondrial p53 translocation was significantly suppressed, accompanied by a significant alleviation in the loss of ΔΨm, cytochrome c release and caspase-9 activation. Furthermore, we also found that generation of reactive oxygen species (ROS) was a critical mediator in heat stress-induced apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat stress-induced p53's mitochondrial translocation, followed by the loss of ΔΨm, cytochrome c release, caspase-9 activation and heat stress-mediated apoptosis. Conclusively, these findings indicate the contribution of the transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC cells induced by oxidative stress in response to intense heat stress.
To maximize the light yield of the liquid scintillator (LS) for the Jiangmen Underground Neutrino Observatory (JUNO), a 20 t LS sample was produced in a pilot plant at Daya Bay. The optical ...properties of the new LS in various compositions were studied by replacing the gadolinium-loaded LS in one antineutrino detector. The concentrations of the fluor, PPO, and the wavelength shifter, bis-MSB, were increased in 12 steps from 0.5 g/L and <0.01 mg/L to 4 g/L and 13 mg/L, respectively. The numbers of total detected photoelectrons suggest that, with the optically purified solvent, the bis-MSB concentration does not need to be more than 4 mg/L. To bridge the one order of magnitude in the detector size difference between Daya Bay and JUNO, the Daya Bay data were used to tune the parameters of a newly developed optical model. Then, the model and tuned parameters were used in the JUNO simulation. This enabled to determine the optimal composition for the JUNO LS: purified solvent LAB with 2.5 g/L PPO, and 1 to 4 mg/L bis-MSB.
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on ...time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI at 90% confidence level are derived as 2×10−32∼7×10−35 cm2 for TI analysis at mχ∼50–180 MeV/c2, and 3×10−32∼9×10−38 cm2 for AM analysis at mχ∼75 MeV/c2–3.0 GeV/c2.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
Summary
We performed a GWAS of trochanter and intertrochanter bone mineral density (BMD) in the Framingham Heart Study and replicated in three independent studies. Our results identified one novel ...locus around the associated variations at chromosomal region 3q13.32 and replicated two loci at chromosomal regions 3p21 and 8q24. Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.
Introduction
Hip trochanter (TRO) and intertrochanter (INT) subregions have important clinical relevance to subtrochanteric and intertrochanteric fractures but have rarely been studied by genome-wide association studies (GWASs).
Methods
Aiming to identify genomic loci associated with BMD variation at TRO and INT regions, we performed a GWAS utilizing the Framingham Heart Study (FHS,
N
= 6,912) as discovery sample and utilized the Women’s Health Initiative (WHI) African-American subsample (
N
= 845), WHI Hispanic subsample (
N
= 446), and Omaha osteoporosis study (
N
= 971), for replication.
Results
Combining the evidence from both the discovery and the replication samples, we identified one novel locus around the associated variations at chromosomal region 3q13.32 (
rs1949542
, discovery
p
= 6.16 × 10
−8
, replication
p
= 2.86 × 10
−4
for INT-BMD; discovery
p
= 1.35 × 10
−7
, replication
p
= 4.16 × 10
−4
for TRO-BMD, closest gene
RP11-384F7.1
). We also replicated two loci at chromosomal regions 3p21 (
rs148725943
, discovery
p
= 6.61 × 10
−7
, replication
p
= 5.22 × 10
−4
for TRO-BMD, closest gene
CTNNB1
) and 8q24 (
rs7839059
, discovery
p
= 2.28 × 10
−7
, replication
p
= 1.55 × 10
−3
for TRO-BMD, closest gene
TNFRSF11B
) that were reported previously. We demonstrated that the effects at both 3q13.32 and 3p21 were specific to the TRO, but not to the femoral neck and spine. In contrast, the effect at 8q24 was common to all the sites.
Conclusion
Our findings provide useful insights that enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.
Magnetic single-atom catalysts (MSAC), due to the intrinsic spin degree of freedom, are of particular importance relative to other conventional SAC for applications in various catalytic processes, ...especially in those cases that involve spin-triplet O2. However, the bottleneck issue in this field is the clustering of the SAC during the processes. Here using first-principles calculations we predict that Mn atoms can be readily confined in the interface of the porous g-C3N4/CeO2(111) heterostructure, forming high-performance MSAC for O2 activation via a delicate synergetic mechanism of charge transfer, mainly provided by the p-block g-C3N4 overlayer mediated by the d-block Mn active site, and spin selection, preserved mainly through active participation of the f-block Ce atoms and/or g-C3N4, which effectively promotes the CO oxidization. Such a recipe is also demonstrated to be valid for V- and Nb-MSACs, which may shed new light on the design of highly efficient MSACs for various important chemical processes wherein spin-selection matters.
This article presents a solution for fatigue recognition through a new deep learning model that has a characteristic input of the power spectrum of an electroencephalogram (EEG) signal. First, four ...rhythms are obtained through the designed FIR filters, and the curve areas of their power spectrum density are coupled into four fatigue indicators. Second, a deep sparse contractive autoencoder network is proposed to learn more local fatigue characteristics, and the recognition results of pilots mental fatigue status are given. Compared with the state-of-the-art models, the results show that our model has good learning performance in extracting local features and fatigue status detection.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
Previous mass screening studies have shown that IgA antibodies against Epstein–Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody ...screening for NPC-specific mortality remains unknown.
A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City.
Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37–1.79, lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09–0.49).
IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis.
NCT00941538.
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