The interactions that lead to the emergence of superconductivity in iron-based materials remain a subject of debate. It has been suggested that electron-electron correlations enhance electron-phonon ...coupling in iron selenide (FeSe) and related pnictides, but direct experimental verification has been lacking. Here we show that the electron-phonon coupling strength in FeSe can be quantified by combining two time-domain experiments into a “coherent lock-in” measurement in the terahertz regime. X-ray diffraction tracks the light-induced femtosecond coherent lattice motion at a single phonon frequency, and photoemission monitors the subsequent coherent changes in the electronic band structure.Comparison with theory reveals a strong enhancement of the coupling strength in FeSe owing to correlation effects. Given that the electron-phonon coupling affects superconductivity exponentially, this enhancement highlights the importance of the cooperative interplay between electron-electron and electron-phonon interactions.
It has been reported that the miR-106b∼25 cluster, a paralog of the miR-17∼92 cluster, possesses oncogenic activities. However, the precise role of each microRNA (miRNA) in the miR-106b∼25 cluster is ...not yet known. In this study, we examined the function of miR-93, one of the microRNAs within the miR-106b∼25 cluster, in angiogenesis and tumor formation. We found that miR-93 enhanced cell survival, promoted sphere formation and augmented tumor growth. Most strikingly, when miR-93-overexpressing U87 cells were co-cultured with endothelial cells, they supported endothelial cell spreading, growth, migration and tube formation. In vivo studies revealed that miR-93-expressing cells induced blood vessel formation, allowing blood vessels to extend to tumor tissues in high densities. Angiogenesis promoted by miR-93 in return facilitated cell survival, resulting in enhanced tumor growth. We further showed that integrin-β8 is a target of miR-93. Higher levels of integrin-β8 are associated with cell death in tumor mass and in human glioblastoma. Silencing of integrin-β8 expression using small interfering RNA promoted cell proliferation, whereas ectopic expression of integrin-β8 decreased cell growth. These findings showed that miR-93 promotes tumor growth and angiogenesis by suppressing, at least in part, integrin-β8 expression. Our results suggest that inhibition of miR-93 function may be a feasible approach to suppress angiogenesis and tumor growth.
The study reported and analyzed the current state of wastewater treatment plants (WWTPs) in urban China from the perspective of treatment technologies, pollutant removals, operating load and effluent ...discharge standards. By the end of 2013, 3508 WWTPs have been built in 31 provinces and cities in China with a total treatment capacity of 1.48×108m3/d. The uneven population distribution between China's east and west regions has resulted in notably different economic development outcomes. The technologies mostly used in WWTPs are AAO and oxidation ditch, which account for over 50% of the existing WWTPs. According to statistics, the efficiencies of COD and NH3–N removal are good in 656 WWTPs in 70 cities. The overall average COD removal is over 88% with few regional differences. The average removal efficiency of NH3–N is up to 80%. Large differences exist between the operating loads applied in different WWTPs. The average operating loading rate is approximately 83%, and 52% of WWTPs operate at loadings of <80%, treating up to 40% of the wastewater generated. The implementation of discharge standards has been low. Approximately 28% of WWTPs that achieved the Grade I-A Discharge Standard of Pollutants for Municipal Wastewater Treatment Plant (GB 18918–2002) were constructed after 2010. The sludge treatment and recycling rates are only 25%, and approximately 15% of wastewater is inefficiently treated. Approximately 60% of WWTPs have capacities of 1×104m3/d–5×104m3/d. Relatively high energy consumption is required for small-scale processing, and the utilization rate of recycled wastewater is low. The challenges of WWTPs are discussed with the aim of developing rational criteria and appropriate technologies for water recycling. Suggestions regarding potential technical and administrative measures are provided.
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•3508 wastewater treatment plants (WWTPs) were summarized.•Population distribution and economic development caused regional difference of WWTPs.•Pollutant removal, operating load, discharge standards in 7 regions were presented.•Suggestions regarding potential technical and administrative measures were provided.
Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy ...composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) ...was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.
We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of ...the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.
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}.
Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety ...and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody.
Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25–75 mg p.o. twice a day; continuous or intermittent), savolitinib (600–800 mg p.o. once a day), or durvalumab (3–10 mg/kg intravenous every 2 weeks).
At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm—diarrhea (75%), rash (58%), nausea (47%); savolitinib arm—nausea (67%), rash (56%), vomiting (50%); durvalumab arm—rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively.
Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated.
NCT02143466.
•Patients with advanced EGFR-mutant NSCLC received osimertinib 80 mg combined with selumetinib, savolitinib or durvalumab.•Feasible dosing strategies were identified for osimertinib plus selumetinib or savolitinib.•Osimertinib plus durvalumab was not feasible due to increased reporting of interstitial lung disease.•Responses were seen in all treatment arms, warranting further analysis of the feasible combinations identified.•Osimertinib-based combinations represent a compelling approach now being investigated broadly to further improve outcomes.
Ferroptosis is a form of regulated non-apoptotic cell death that has been implicated in several disease contexts. A better understanding of the ferroptotic death mechanism could lead to the ...development of new therapeutics for degenerative diseases, and a better understanding of how to induce ferroptosis in specific tumor contexts. We performed an unbiased genome-wide siRNA screen to find genetic suppressors of ferroptosis. We determined that loss of CARS, the cysteinyl-tRNA synthetase, suppresses ferroptosis induced by erastin, which inhibits the cystine-glutamate antiporter known as system xc(-). Knockdown of CARS inhibited erastin-induced death by preventing the induction of lipid reactive oxygen species, without altering iron homeostasis. Knockdown of CARS led to the accumulation of cystathionine, a metabolite on the transsulfuration pathway, and upregulated genes associated with serine biosynthesis and transsulfuration. In addition, inhibition of the transsulfuration pathway resensitized cells to erastin, even after CARS knockdown. These studies demonstrate a new mechanism of resistance to ferroptosis and may lead to strategies for inducing and suppressing ferroptosis in diverse contexts.
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