Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation and are associated with the development of cancers. To investigate the important role and mechanism of lncRNAs in the ...progression of gastric cancer, we screened lncRNAs in gastric cancer tissues and corresponding adjacent tissues, and assessed the effects on gastric cancer. Here, we report that BC032469, a novel lncRNA, expressed highly in gastric cancer tissues, and the upregulation was clinically associated with larger tumor size, poor differentiation and shorter survival of gastric cancer patients. Downregulation of BC032469 resulted in a significant inhibition of proliferation in vitro and in vivo. Mechanistically, BC032469 could directly bind to miR-1207-5p and effectively functioned as a sponge for miR-1207-5p to modulate the derepression of hTERT. Thus, BC032469 may function as a ceRNA to impair miR-1207-5p-dependent hTERT downregulation, suggesting that it may be clinically valuable as a poor prognostic biomarker of gastric cancer.
Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung ...cancer (NSCLC). It is critical to analyze RET mutants resistant to these drugs and unravel the molecular basis to improve patient outcomes.
Cell-free DNAs (cfDNAs) were analyzed in a RET-mutant medullary thyroid cancer (MTC) patient and a CCDC6-RET fusion NSCLC patient who had dramatic response to selpercatinib and later developed resistance. Selpercatinib-resistant RET mutants were identified and cross-profiled with pralsetinib in cell cultures. Crystal structures of RET-selpercatinib and RET-pralsetinib complexes were determined based on high-resolution diffraction data collected with synchrotron radiation.
RETG810C/S mutations at the solvent front and RETY806C/N mutation at the hinge region were found in cfDNAs of an MTC patient with RETM918T/V804M/L, who initially responded to selpercatinib and developed resistance. RETG810C mutant was detected in cfDNAs of a CCDC6-RET-fusion NSCLC patient who developed acquired resistance to selpercatinib. Five RET kinase domain mutations at three non-gatekeeper residues were identified from 39 selpercatinib-resistant cell lines. All five selpercatinib-resistant RET mutants were cross-resistant to pralsetinib. X-ray crystal structures of the RET-selpercatinib and RET-pralsetinib complexes reveal that, unlike other TKIs, these two RET TKIs anchor one end in the front cleft and wrap around the gate wall to access the back cleft.
RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.
•Resistance to selpercatinib and pralsetinib are found at the solvent front and hinge sites of the RET kinase domain.•The identified selpercatinib-resistant RET mutants are cross-resistant to pralsetinib.•Selpercatinib and pralsetinib use an unprecedented binding mode to dock into the RET kinase.•The new kinase inhibitor binding mode avoids the interference from gatekeeper mutations but remains vulnerable to non-gatekeeper mutations.
Cracks in solid-state materials are typically irreversible. Here we report electrically reversible opening and closing of nanoscale cracks in an intermetallic thin film grown on a ferroelectric ...substrate driven by a small electric field (~0.83 kV/cm). Accordingly, a nonvolatile colossal electroresistance on-off ratio of more than 10
is measured across the cracks in the intermetallic film at room temperature. Cracks are easily formed with low-frequency voltage cycling and remain stable when the device is operated at high frequency, which offers intriguing potential for next-generation high-frequency memory applications. Moreover, endurance testing demonstrates that the opening and closing of such cracks can reach over 10
cycles under 10-μs pulses, without catastrophic failure of the film.
Fava bean peels, Vicia faba (FBP) are investigated as biosorbents for the removal of Methylene Blue (MB) dye from aqueous solutions through a novel and efficient sorption process utilizing ...ultrasonic-assisted (US) shaking. Ultrasonication remarkably enhanced sorption rate relative to conventional (CV) shaking, while maintaining the same sorption capacity. Ultrasonic sorption rate amounted to four times higher than its conventional counterpart at 3.6 mg/L initial dye concentration, 5 g/L adsorbent dose, and pH 5.8. Under the same adsorbent dose and pH conditions, percent removal ranged between 70-80% at the low dye concentration range (3.6-25 mg/L) and reached about 90% at 50 mg/L of the initial dye concentration. According to the Langmuir model, maximum sorption capacity was estimated to be 140 mg/g. A multiple linear regression statistical model revealed that adsorption was significantly affected by initial concentration, adsorbent dose and time. FBP could be successfully utilized as a low-cost biosorbent for the removal of MB from wastewater via US biosorption as an alternative to CV sorption. US biosorption yields the same sorption capacities as CV biosorption, but with significant reduction in operational times.
We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon ...number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.
We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five ...center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrts=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
A novel nano‐packing material with lower relative humidity, oxygen transmission rate and high longitudinal strength was synthesized by blending polyethylene with nano‐powder (nano‐Ag, kaolin, anatase ...TiO2, rutile TiO2), and its effect on preservation quality of strawberry fruits (Fragaria ananassa Duch. cv Fengxiang) was investigated during storage at 4 °C. Results showed that nano‐packaging was able to maintain the sensory, physicochemical, and physiological quality of strawberry fruits at a higher level compared with the normal packing (polyethylene bags). After a 12‐d storage, decreases in the contents of total soluble solids, titratable acidity, and ascorbic acid of nano‐packing were significantly inhibited. Meanwhile, decay rate, anthocyanin, and malondialdehyde contents were decreased to 16.7%, 26.3 mg/100g, 66.3 μmol/g for nano‐packing and 26.8%, 31.9 mg/100g, 75.4 μmol/g for normal packing; polyphenoloxidase (PPO) and pyrogallol peroxidase (POD) activities were significantly lower in nano‐packing than the control. These data indicated that the nano‐packaging might provide an attractive alternative to improve preservation quality of the strawberry fruits during extended storage.
Practical Application: Nano‐packing exhibited identified quality benefits applicable to the preservation of fresh strawberry. Furthermore, nano‐packing has the advantages of simple processing and feasibility to be industrialized in contrast with other storages. Thus, the utilization of nano‐packing will likely assist commercial producers and retailers in extending the shelf life of products over a broader range in the future.
Regulations play an important role in assuring the construction quality. However, due to the large amount of regulation needs considered, the construction quality compliance checking against ...regulations can be cumbersome/time-consuming and error prone. In order to give more computerized support to the construction quality compliance checking against regulations, an ontology-based semantic modeling approach of regulation constraints is explored. A meta model for construction quality inspection and evaluation i.e. CQIEOntology is proposed in this paper. Based on CQIEontology, the regulation constraints are modeled into OWL axioms and SWRL rules. By these OWL axioms and SWRL rules, the regulation provisions imposed on construction quality inspection can be translated into a set of inspection tasks, and get associated with the specific construction tasks. Once the construction starts, the applicable inspection tasks, including a series of quality checking and evaluation, will be reminded and recommended. Obviously, the proposed approach facilitates taking the construction quality compliance checking as a paralleling activity to the construction rather than an afterthought, and helps the inspectors in quality inspection. Finally, the approach is demonstrated in Protégé 3.4.6 through case studies based on regulation examples taken from “Code for Acceptance of Construction Quality of Building Foundation (GB50202-2002) and the validation and discussion are given for it.”
► A meta model for construction quality inspection and evaluation is proposed. ► Ontology and semantic technologies are selected to model the relevant knowledge. ► The approach is tested and assessed. ► Helping inspectors implement quality checking against relevant regulations.
Proxy records of temperature from the Atlantic clearly show that the Younger Dryas was an abrupt climate change event during the last deglaciation, but records of hydroclimate are underutilized in ...defining the event. Here we combine a new hydroclimate record from Palawan, Philippines, in the tropical Pacific, with previously published records to highlight a difference between hydroclimate and temperature responses to the Younger Dryas. Although the onset and termination are synchronous across the records, tropical hydroclimate changes are more gradual (>100 years) than the abrupt (10-100 years) temperature changes in the northern Atlantic Ocean. The abrupt recovery of Greenland temperatures likely reflects changes in regional sea ice extent. Proxy data and transient climate model simulations support the hypothesis that freshwater forced a reduction in the Atlantic meridional overturning circulation, thereby causing the Younger Dryas. However, changes in ocean overturning may not produce the same effects globally as in Greenland.
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