Patients with severe chronic obstructive pulmonary disease (COPD) are at higher risk of developing invasive pulmonary aspergillosis (IPA). However, there are limited data for this disease. To ...evaluate risk factors and the clinical characteristics of IPA in COPD patients, we conducted a hospital-based, retrospective case-control study of 30 COPD patients with IPA and 60 COPD control patients without IPA. Patients in the case group were significantly more likely to have concurrent co-morbidities than controls. Of the IPA patients, 65.4% had worsening radiological findings vs. 11.4% in the control group (p <0.001). IPA in COPD was associated with a higher proportion of mechanical ventilation (43.3% vs. 5%; p <0.001), a longer hospital stay duration (45.8 ± 39.1 days vs. 18.4 ± 11.8 days; p <0.001), and higher mortality (43.3% vs. 11.4%; p <0.001). Systemic use of steroids in the stable phase, treatment with three or more antibiotics during hospitalization and antibiotic treatment longer than 10 days were independent risk factors associated with IPA. COPD patients with obvious dyspnoea, antibiotic-resistant lower respiratory tract infection and repeated detection of Aspergillus in sputum should be considered for the possibility of IPA.
In an attempt to tailor low-cost, precious-metal-free electrocatalysts for water electrolysis in acid, molybdenum carbide ( beta -Mo sub(2)C) nanoparticles are prepared by in situcarburization of ...ammonium molybdate on carbon nanotubes and XC-72R carbon black without using any gaseous carbon source. The formation of Mo sub(2)C is investigated by thermogravimetry and in situX-ray diffraction. X-ray absorption analysis reveals that Mo sub(2)C nanoparticles are inlaid or anchored into the carbon supports, and the electronic modification makes the surface exhibit a relatively moderate Mo-H bond strength. It is found that carbon nanotube-supported Mo sub(2)C showed superior electrocatalytic activity and stability in the hydrogen evolution reaction (HER) compared to the bulk Mo sub(2)C. An overpotential of 63 mV for driving 1 mA cm super(-2) of current density was measured for the nanotube-supported Mo sub(2)C catalysts; this exceeds the activity of analogous Mo sub(2)C catalysts. The enhanced electrochemical activity is facilitated by unique effects of the anchored structure coupled with the electronic modification.
Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in ...breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH
subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.
Abstract
Background
Inactivation of the tumor suppressor p53 is critical for pathogenesis of glioma, in particular glioblastoma multiforme (GBM). MDM2, the main negative regulator of p53, binds to ...and forms a stable complex with p53 to regulate its activity. Hitherto, it is unclear whether the stability of the p53/MDM2 complex is affected by lncRNAs, in particular circular RNAs that are usually abundant and conserved, and frequently implicated in different oncogenic processes.
Methods
RIP-seq and RIP-qPCR assays were performed to determine the most enriched lncRNAs (including circular RNAs) bound by p53, followed by bioinformatic assays to estimate the relevance of their expression with p53 signaling and gliomagenesis. Subsequently, the clinical significance of
CDR1as
was evaluated in the largest cohort of Chinese glioma patients from CGGA (
n
= 325), and its expression in human glioma tissues was further evaluated by RNA FISH and RT-qPCR, respectively. Assays combining RNA FISH with protein immunofluorescence were performed to determine co-localization of
CDR1as
and p53, followed by CHIRP assays to confirm RNA-protein interaction. Immunoblot assays were carried out to evaluate protein expression, p53/MDM2 interaction and p53 ubiquitination in cells in which
CDR1as
expression was manipulated. After
AGO2
or
Dicer
was knocked-down to inhibit miRNA biogenesis, effects of
CDR1as
on p53 expression, stability and activity were determined by immunoblot, RT-qPCR and luciferase reporter assays. Meanwhile, impacts of
CDR1as
on DNA damage were evaluated by flow cytometric assays and immunohistochemistry. Tumorigenicity assays were performed to determine the effects of
CDR1as
on colony formation, cell proliferation, the cell cycle and apoptosis (in vitro), and on tumor volume/weight and survival of nude mice xenografted with GBM cells (in vivo).
Results
CDR1as
is found to bind to p53 protein.
CDR1as
expression decreases with increasing glioma grade and it is a reliable independent predictor of overall survival in glioma, particularly in GBM. Through a mechanism independent of acting as a miRNA sponge,
CDR1as
stabilizes p53 protein by preventing it from ubiquitination.
CDR1as
directly interacts with the p53 DBD domain that is essential for MDM2 binding, thus disrupting the p53/MDM2 complex formation. Induced upon DNA damage,
CDR1as
may preserve p53 function and protect cells from DNA damage. Significantly,
CDR1as
inhibits tumor growth in vitro and in vivo, but has little impact in cells where p53 is absent or mutated.
Conclusions
Rather than acting as a miRNA sponge,
CDR1as
functions as a tumor suppressor through binding directly to p53 at its DBD region to restrict MDM2 interaction. Thus,
CDR1as
binding disrupts the p53/MDM2 complex to prevent p53 from ubiquitination and degradation.
CDR1as
may also sense DNA damage signals and form a protective complex with p53 to preserve p53 function. Therefore,
CDR1as
depletion may play a potent role in promoting tumorigenesis through down-regulating p53 expression in glioma. Our results broaden further our understanding of the roles and mechanism of action of circular RNAs in general and
CDR1as
in particular, and can potentially open up novel therapeutic avenues for effective glioma treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electronic structures of graphene oxide (GO) and hydro-thermally reduced graphene oxides (rGOs) processed at low temperatures (120-180°C) were studied using X-ray absorption near-edge structure ...(XANES), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS). C K-edge XANES spectra of rGOs reveal that thermal reduction restores C = C sp(2) bonds and removes some of the oxygen and hydroxyl groups of GO, which initiates the evolution of carbonaceous species. The combination of C K-edge XANES and Kα XES spectra shows that the overlapping π and π* orbitals in rGOs and GO are similar to that of highly ordered pyrolytic graphite (HOPG), which has no band-gap. C Kα RIXS spectra provide evidence that thermal reduction changes the density of states (DOSs) that is generated in the π-region and/or in the gap between the π and π* levels of the GO and rGOs. Two-dimensional C Kα RIXS mapping of the heavy reduction of rGOs further confirms that the residual oxygen and/or oxygen-containing functional groups modify the π and σ features, which are dispersed by the photon excitation energy. The dispersion behavior near the K point is approximately linear and differs from the parabolic-like dispersion observed in HOPG.
Soft and conformable wearable electronics require stretchable semiconductors, but existing ones typically sacrifice charge transport mobility to achieve stretchability. We explore a concept based on ...the nanoconfinement of polymers to substantially improve the stretchability of polymer semiconductors, without affecting charge transport mobility. The increased polymer chain dynamics under nanoconfinement significantly reduces the modulus of the conjugated polymer and largely delays the onset of crack formation under strain. As a result, our fabricated semiconducting film can be stretched up to 100% strain without affecting mobility, retaining values comparable to that of amorphous silicon. The fully stretchable transistors exhibit high biaxial stretchability with minimal change in on current even when poked with a sharp object. We demonstrate a skinlike finger-wearable driver for a light-emitting diode.
Summary
Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic ...vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age.
Introduction
The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs.
Methods
We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs.
Results
During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (
p
= 0.003), female (
p
= 0.024), advanced age (≥ 75 years;
p
< 0.001), lower BMD (
p
< 0.001), lower BMI (
p
= 0.01), TL junction (vertebral levels at the thoracolumbar junction) (
p
= 0.01), cardiopulmonary comorbidity (
p
= 0.042), and hypoalbuminemia (
p
= 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069–4.824,
p
= 0.033), lower BMD (OR 1.968; 95% CI 1.350–2.868,
p
< 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246–4.744,
p
= 0.009), and female sex (OR 4.666; 95% CI 1.400–15.552,
p
= 0.012) were independent risk predictors of OVCRFs.
Conclusions
Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.
Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning ...their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa
Cu
O
after the quench of superconductivity by an infrared laser pulse. We observe a nonthermal response of the CDW order characterized by a near doubling of the correlation length within ≈1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDWs manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations.
As an important topological index, the fifth geometric-arithmetic index is used to test the chemical properties of chemical compounds, nanomaterials and drugs. In this paper, by means of graph ...structure analysis and edge dividing technology, the formulate for calculating the fifth geometric-arithmetic index of bridge graph is given. Furthermore, we present the fifth geometric-arithmetic index of carbon nanocones
.
Quantum heat engines are expected to outperform the classical counterparts due to quantum coherences involved. Here we experimentally execute a single-ion quantum heat engine and demonstrate, for the ...first time, the dynamics and the enhanced performance of the heat engine originating from the Liouvillian exceptional points (LEPs). In addition to the topological effects related to LEPs, we focus on thermodynamic effects, which can be understood by the Landau-Zener-Stückelberg process under decoherence. We witness a positive net work from the quantum heat engine if the heat engine cycle dynamically encircles a LEP. Further investigation reveals that a larger net work is done when the system is operated closer to the LEP. We attribute the enhanced performance of the quantum heat engine to the Landau-Zener-Stückelberg process, enabled by the eigenenergy landscape in the vicinity of the LEP, and the exceptional point-induced topological transition. Therefore, our results open new possibilities toward LEP-enabled control of quantum heat engines and of thermodynamic processes in open quantum systems.
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