Telomerase activation through induction of telomerase reverse transcriptase (hTERT) contributes to malignant transformation by stabilizing telomeres. Clinical studies demonstrate that higher hTERT ...expression is associated with cancer progression and poor outcomes, but the underlying mechanism is unclear. Because epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are key factors in cancer metastasis and relapse, and hTERT has been shown to exhibit multiple biological activities independently of its telomere-lengthening function, we address a potential role of hTERT in EMT and CSCs using gastric cancer (GC) as a model. hTERT overexpression promotes, whereas its inhibition suppresses, EMT and stemness of GC cells, respectively. Transforming growth factor (TGF)-β1 and β-catenin-mediated EMT was abolished by small interfering RNA depletion of hTERT expression. hTERT interacts with β-catenin, enhances its nuclear localization and transcriptional activity, and occupies the β-catenin target vimentin promoter. All these hTERT effects were independent of its telomere-lengthening function or telomerase activity. hTERT and EMT marker expression correlates positively in GC samples. Mouse experiments demonstrate the in vivo stimulation of hTERT on cancer cell colonization. Collectively, hTERT stimulates EMT and induces stemness of cancer cells, thereby promoting cancer metastasis and recurrence. Thus, targeting hTERT may prevent cancer progression by inhibiting EMT and CSCs.
The electrochemical conversion of CO2 and H2O into liquid fuel is ideal for high-density renewable energy storage and could provide an incentive for CO2 capture. However, efficient electrocatalysts ...for reducing CO2 and its derivatives into a desirable fuel are not available at present. Although many catalysts can reduce CO2 to carbon monoxide (CO), liquid fuel synthesis requires that CO is reduced further, using H2O as a H(+) source. Copper (Cu) is the only known material with an appreciable CO electroreduction activity, but in bulk form its efficiency and selectivity for liquid fuel are far too low for practical use. In particular, H2O reduction to H2 outcompetes CO reduction on Cu electrodes unless extreme overpotentials are applied, at which point gaseous hydrocarbons are the major CO reduction products. Here we show that nanocrystalline Cu prepared from Cu2O ('oxide-derived Cu') produces multi-carbon oxygenates (ethanol, acetate and n-propanol) with up to 57% Faraday efficiency at modest potentials (-0.25 volts to -0.5 volts versus the reversible hydrogen electrode) in CO-saturated alkaline H2O. By comparison, when prepared by traditional vapour condensation, Cu nanoparticles with an average crystallite size similar to that of oxide-derived copper produce nearly exclusive H2 (96% Faraday efficiency) under identical conditions. Our results demonstrate the ability to change the intrinsic catalytic properties of Cu for this notoriously difficult reaction by growing interconnected nanocrystallites from the constrained environment of an oxide lattice. The selectivity for oxygenates, with ethanol as the major product, demonstrates the feasibility of a two-step conversion of CO2 to liquid fuel that could be powered by renewable electricity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Historically, the majority of new drugs have been generated from natural products (secondary metabolites) and from compounds derived from natural products. During the past 15 years, pharmaceutical ...industry research into natural products has declined, in part because of an emphasis on high-throughput screening of synthetic libraries. Currently there is substantial decline in new drug approvals and impending loss of patent protection for important medicines. However, untapped biological resources, "smart screening" methods, robotic separation with structural analysis, metabolic engineering, and synthetic biology offer exciting technologies for new natural product drug discovery. Advances in rapid genetic sequencing, coupled with manipulation of biosynthetic pathways, may provide a vast resource for the future discovery of pharmaceutical agents.
By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally ...produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.
With the development of antitumor therapies, different treatment methods including monotherapy and combined therapy have achieved clinical efficacy in advanced epidermal growth factor receptor (EGFR) ...mutant non-small cell lung cancer (NSCLC) patients. Exon 19 deletion (ex19del) and exon 21 L858R mutation are common sensitive subtypes of EGFR mutation. However, potential distinct mechanisms are found from several dimensions including molecular structures, biological behaviors, concomitant mutations, resistance mechanisms and tumor mutation burdens. More evidence indicates the prognostic difference of EGFR subgroups. This review focused on the progress of potential distinct mechanisms and outcomes in clinical trials of advanced NSCLC patients with ex19del or exon 21 L858R mutation.
Bacterial ocular infections are common. Traditional culture and molecular biological methods have obvious limitations to identify the conjunctival microbiota, while metagenomic studies can avoid the ...defects of these methods. We used the Illumina high-throughput sequencing technology (MiSeq Illumina Sequencing Platform) to sequence the 16S rDNA V3–V4 hypervariable region of all bacteria in conjunctival swab samples. The operational taxonomic units were obtained from the sequences. The bioinformatic analyses of taxonomy, abundance and alpha diversity were performed. A total of 840 373 high-quality sequencing reads were generated from 31 conjunctival samples. The number of the species operational taxonomic units ranged from 159 to 2042, indicating high microbial diversity. The combined bacterial community was classified into 25 phyla and 526 distinct genera. At the genus level, Corynebacterium (28.22%), Pseudomonas (26.75%), Staphylococcus (5.28%), Acinetobacter (4.74%), Streptococcus (2.85%), Millisia (2.16%), Anaerococcus (1.86%), Finegoldia (1.68%), Simonsiella (1.48%) and Veillonella (1.00%) accounted for over 76% of the microbial community, possibly representing the core genera in normal conjunctival microbiota. The composition and diversity of microbiota in the normal adult human conjunctiva were characterized using high-throughput sequencing. A framework for investigating potential roles played by the diverse microbiota in disease related with the ocular surface was provided.
Weyl semimetals are crystalline solids that host emergent relativistic Weyl fermions and have characteristic surface Fermi-arcs in their electronic structure. Weyl semimetals with broken time ...reversal symmetry are difficult to identify unambiguously. In this work, using angle-resolved photoemission spectroscopy, we visualized the electronic structure of the ferromagnetic crystal Co
Sn
S
and discovered its characteristic surface Fermi-arcs and linear bulk band dispersions across the Weyl points. These results establish Co
Sn
S
as a magnetic Weyl semimetal that may serve as a platform for realizing phenomena such as chiral magnetic effects, unusually large anomalous Hall effect and quantum anomalous Hall effect.
Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer's disease through the antagonism of adenosine A2A receptors (A2ARs). To ...test if A2AR activation in the hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine-binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-mitogen-activated protein kinase (p-MAPK) (but not cGMP) levels in human embryonic kidney 293 (HEK293) cells, which was abolished by a point mutation at the C terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and p-MAPK signaling in HEK293 cells, of p-MAPK in the nucleus accumbens and of c-Fos/phosphorylated-CREB (p-CREB) in the hippocampus, and similarly enhanced long-term potentiation in the hippocampus. Remarkably, optoA2AR activation triggered a preferential p-CREB signaling in the hippocampus and impaired spatial memory performance, while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in the hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops prompts the possibility of targeting the intracellular A2AR-interacting partners to selectively control different neuropsychiatric behaviors.
Economical, environmental and legislative drivers have recently raised the awareness of energy consumption and the associated environmental impact of manufacturing processes. A reliable prediction of ...unit process energy consumption will enable industry to develop potential energy saving strategies during product design and process planning stages. This paper presents an empirical model to characterize the relationship between energy consumption and process variables for material removal processes. The methodology has been tested and validated on a number of turning and milling machine tools. The model presented predicts the energy consumption of manufacturing processes with an accuracy of more than 90%.
Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing Joung, Julia; Ladha, Alim; Saito, Makoto ...
New England journal of medicine/The New England journal of medicine,
10/2020, Letnik:
383, Številka:
15
Journal Article
Recenzirano
Odprti dostop
A new method for the detection of SARS-CoV-2 combines simplified extraction of RNA with isothermal amplification and CRISPR (clustered regularly interspaced short palindromic repeats)–mediated ...detection. Testing of 402 samples indicated a sensitivity of 93.1% and a specificity of 98.5%.
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