The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term ...adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
Plasma free fatty acids levels are increased in subjects with obesity and type 2 diabetes, playing detrimental roles in the pathogenesis of atherosclerosis and cardiovascular diseases. Increasing ...evidence showing that dysfunction of the vascular endothelium, the inner lining of the blood vessels, is the key player in the pathogenesis of atherosclerosis. In this review, we aimed to summarize the roles and the underlying mechanisms using the evidence collected from clinical and experimental studies about free fatty acid-mediated endothelial dysfunction. Because of the multifaceted roles of plasma free fatty acids in mediating endothelial dysfunction, elevated free fatty acid level is now considered as an important link in the onset of endothelial dysfunction due to metabolic syndromes such as diabetes and obesity. Free fatty acid-mediated endothelial dysfunction involves several mechanisms including impaired insulin signaling and nitric oxide production, oxidative stress, inflammation and the activation of the renin-angiotensin system and apoptosis in the endothelial cells. Therefore, targeting the signaling pathways involved in free fatty acid-induced endothelial dysfunction could serve as a preventive approach to protect against the occurrence of endothelial dysfunction and the subsequent complications such as atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The optical properties of the symmetric salamo-like chemical probe (H
2
CS) of Cu
2+
were studied in EtOH/H
2
O (1:1, v/v) solution by UV-Vis and fluorescence spectroscopy. In the fluorescence ...spectrum, the coordination of Cu
2+
with H
2
CS results in fluorescence quenching owing to the paramagnetic nature of Cu
2+
ions. The binding constant of Cu
2+
to the H
2
CS sensor was calculated as 1.17 × 10
11
M
–1
and LOD was obtained as 5.3 × 10
–8
M. When Cu
2+
ions were added, the UV-Vis spectra changed, obviously due to the electron transfer from sensor to metal bond, and a new absorption band appeared at 372 nm. When the ethylenediaminetetraacetic acid (EDTA) solution was added to the H
2
CS–Cu
2+
solution, causing a large binding constant, with EDTA releasing the free sensor molecule and finally achieving a fluorescence shutdown phenomenon.
We present measurements of a topological property, the Chern number (C_{1}), of a closed manifold in the space of two-level system Hamiltonians, where the two-level system is formed from a ...superconducting qubit. We manipulate the parameters of the Hamiltonian of the superconducting qubit along paths in the manifold and extract C_{1} from the nonadiabatic response of the qubit. By adjusting the manifold such that a degeneracy in the Hamiltonian passes from inside to outside the manifold, we observe a topological transition C_{1}=1→0. Our measurement of C_{1} is quantized to within 2% on either side of the transition.
Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key ...regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.
Chromosomal aneuploidy is the major reason why couples opt for prenatal diagnosis. Current methods for definitive diagnosis rely on invasive procedures, such as chorionic villus sampling and ...amniocentesis, and are associated with a risk of fetal miscarriage. Fetal DNA has been found in maternal plasma but exists as a minor fraction among a high background of maternal DNA. Hence, quantitative perturbations caused by an aneuploid chromosome in the fetal genome to the overall representation of sequences from that chromosome in maternal plasma would be small. Even with highly precise single molecule counting methods such as digital PCR, a large number of DNA molecules and hence maternal plasma volume would need to be analyzed to achieve the necessary analytical precision. Here we reasoned that instead of using approaches that target specific gene loci, the use of a locus-independent method would greatly increase the number of target molecules from the aneuploid chromosome that could be analyzed within the same fixed volume of plasma. Hence, we used massively parallel genomic sequencing to quantify maternal plasma DNA sequences for the noninvasive prenatal detection of fetal trisomy 21. Twenty-eight first and second trimester maternal plasma samples were tested. All 14 trisomy 21 fetuses and 14 euploid fetuses were correctly identified. Massively parallel plasma DNA sequencing represents a new approach that is potentially applicable to all pregnancies for the noninvasive prenatal diagnosis of fetal chromosomal aneuploidies.
Abstract
The nature of the so-called “changing-look” (CL) active galactic nucleus (AGN), which is characterized by spectral-type transitions within ∼10 yr, remains an open question. As the first in ...our series of studies, we attempt here to understand the CL phenomenon from the view of the coevolution of AGNs and their host galaxies (i.e., if CL-AGNs are at a specific evolutionary stage) by focusing on the SDSS local “partially obscured” AGNs in which the stellar population of the host galaxy can be easily measured in the integrated spectra. A spectroscopic follow-up program using the Xinglong 2.16 m, Lick/Shane 3 m, and Keck 10 m telescopes enables us to identify in total nine CL-AGNs from a sample of 59 candidates selected by their mid-infrared variability. Detailed analysis of these spectra shows that the host galaxies of the CL-AGNs are biased against young stellar populations and tend to be dominated by intermediate-age stellar populations. This motivates us to propose that CL-AGNs are probably particular AGNs at a specific evolutionary stage, such as a transition stage from “feast” to “famine” fueling of the supermassive black hole. In addition, we reinforce the previous claim that CL-AGNs tend to be biased against both a high Eddington ratio and a high bolometric luminosity, suggesting that the disk-wind broad-line-region model is a plausible explanation of the CL phenomenon.
Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank ...enriched in EOCRCs.
We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed.
We observed a striking diversity of molecular phenotypes, including
fusions. Transcriptionally,
fusion organoids resembled normal colon organoids and were distinct from
mutant organoids, with high
and low
expression. Single cell transcriptome analysis confirmed the similarity between
fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the
mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of
in normal human colon organoids led to upregulation of PTK7 protein and suppression of
, but less so with an engineered
mutation. The frequent co-occurrence of
fusions with
or
mutation was confirmed in TCGA database searches.
mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time.
These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.
In the present study, a novel TiO2-based coating containing nanosized hydroxyapatite (n-HA) has been formed on commercially available Ti–6Al–4V (Grade 5) alloy substrates by the Plasma Electrolytic ...Oxidation (PEO) technique. The TiO2:n-HA coating deposition was provided in an aqueous solution of disodium hydrogen phosphate containing suspended hydroxyapatite nanoparticles under a pulsed bipolar current mode. The surface morphology of the formed coatings has been examined by Scanning Electron Microscopy (SEM), while the element composition of the coatings has been determined by Energy Dispersive X-ray analysis (EDS). The presence of HA nanoparticles within the formed coatings has been analyzed by Fourier Transform Infrared Spectroscopy (FTIR). The corrosion resistance of the TiO2:n-HA coatings has been studied by electrochemical methods, including open circuit potential, potentiodynamic polarization and electrochemical impedance spectroscopy, and compared to the corrosion behavior of bare titanium. The results indicate that the formed PEO coatings exhibit a porous network structure with embedded n-HA particles uniformly distributed over the entire surface of the coatings. The PEO coated samples showed substantially higher corrosion resistance compared to the bare Ti–6Al–4V substrate material. The PEO-formed TiO2:n-HA layers reduce the corrosion of titanium alloy implant materials and can be used as a bioactive biomimetic coating to enhance implant surface bioactivity and osseointegration.
•Process of forming TiO2:n-HA coatings on titanium alloy by PEO is presented.•Characterization and corrosion evaluation of TiO2:n-HA coatings are given.•The TiO2:n-HA coated Ti6Al4V alloy possesses higher corrosion resistance.•The layer exhibits high resistance to the onset of localized pitting corrosion.•EIS analysis confirmed a presence of a bi-layered structure.
Community wastewater management systems (CWMS) are small-scale wastewater treatment systems typically in regional and rural areas with less sophisticated treatment processes and often managed by ...local governments or communities. Research and industrial applications have demonstrated that online UV-Vis sensors have great potential for improving wastewater monitoring and treatment processes. Existing studies on the development of surrogate parameters with models from spectral data for wastewater were largely limited to lab-based. In contrast, industrial applications of these sensors have primarily targeted large wastewater treatment plants (WWTPs), leaving a gap in research for small-scale WWTPs. This paper demonstrates the suitability of using a field-based online UV-Vis sensor combined with advanced data analytics for CWMSs as an early warning for process upset to support sustainable operations. An industry case study is provided to demonstrate the development of surrogate monitoring parameters for total suspended solids (TSSs) and chemical oxygen demand (COD) using the UV-Vis spectral data from an online UV-Vis sensor. Absorbances at a wavelength of 625 nm (UV
) and absorbances at a wavelength of 265 nm (UV
) were identified as surrogate parameters to measure TSSs and COD, respectively. This study contributes to the improvement of WWTP performance with a continuous monitoring system by developing a process monitoring framework and optimization strategy.
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