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Light regulates anthocyanins synthesis in plants. Upon exposure to visible light, the inhibition of photosynthetic electron transfer significantly lowered the contents of anthocyanins and the expression levels of key genes involved in anthocyanins synthesis in plum fruit peel. Meanwhile, the expression levels of PsmMDH2 (encoding the malate dehydrogenase in mitochondria) and PschMDH (encoding the malate dehydrogenase in chloroplasts) decreased significantly. The contents of anthocyanins and the levels of the key genes involved in anthocyanin synthesis decreased significantly with the treatment of 1‐MCP (an inhibitor of ethylene perception) but were enhanced by the exogenous application of ethylene. The ethylene treatment could also recover the anthocyanin synthesis capacity lowered by the photosynthetic electron transfer inhibition. Silencing PsmMDH2 and PschMDH significantly lowered the contents of anthocyanins in plum fruit. At low temperature, visible light irradiation induced anthocyanin accumulation in Arabidopsis leaves. However, the mmdh, chmdh, and etr1‐1 mutants had significantly lower anthocyanins content and expressions of the key genes involved in anthocyanins synthesis compared to wild type. Overall, the present study demonstrates that both photosynthesis and respiration were involved in the regulation of anthocyanin synthesis in visible light. The visible light regulates anthocyanin synthesis by controlling the malate metabolism via MDHs and the ethylene signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Signaling through mTOR and somatostatin pathway is implicated in thyroid cancer development. Method: We evaluated everolimus, an mTOR inhibitor and pasireotide, a multi receptor somatostatin analogue as potential therapy of thyroid cancer focusing on the in vitro and in vivo efficacy, as well as possible mechanism to explain any observed interaction. Results: Both everolimus and pasireotide inhibit the growth of thyroid cancer cell lines in vitro with varied efficacy that correlates with tumor origin and somatostatin receptor (SSTR) expression profile of the cell lines. In vitro activity of everolimus show positive correlation with the expression of SSTR types 1, 4 and 5 (CC: 0.9; 0.85, 0.87) while pasireotide activity show negative correlation with SSTR2 (CC: -0.87). Although there is greater modulation of pS6 when pasireotide is combined with everolimus, there is no significant abrogation of the expected feedback upregulation of AKT induced by everolimus. Also, the combination is not significantly better than each agent alone in short and long term in vitro assays. Continuous administration of everolimus at a low dose as opposed to high intermittent dosing schedule has greater antitumor efficacy against thyroid cancer xenografts in vivo. Pasireotide LAR has modest in vivo efficacy and the combination of everolimus and pasireotide LAR achieve greater tumor growth inhibition than each agent alone in TPC-1 xenograft model of thyroid cancer (p = 0.048). Conclusion: Our findings provide support for the clinical evaluation of everolimus and pasireotide in thyroid cancer and other neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

In this paper, we consider the stability of three-dimensional compressible viscous fluid around the plane Couette flow in the presence of a uniform transverse magnetic field and show that the uniform transverse magnetic field has a stabilizing effect on the plane Couette flow. Namely, for a sufficiently large Hartmann number, the compressible viscous plane Couette flow is nonlinear stable for small Mach number and arbitrary Reynolds number so long as the initial perturbation is small enough. [ABSTRACT FROM AUTHOR]

In this paper, we study the steady flows to the compressible Euler-Poisson system for semiconductors with the nonzero angular velocity in a radially symmetric way in an annulus. The main purpose here is to elucidate the effect of the angular velocity in the structure of the steady flows. We show the well-posedness of all kinds of types of radially symmetric spiral flows including radial subsonic/supersonic/transonic flows, and further give a specific classification of the flow patterns under the assumption of various boundary conditions at the inner and the outer circle. Additionally, different from the purely radial case, the uniqueness of radial subsonic flow can not be obtained due to the nonlocal effect caused by the angular velocity, consequently we prove the uniqueness of the radial subsonic solution in the case without the semiconductor effect or with a small current assumption. Moreover, some new patterns of spiral flows with or without shock are observed, such as a smooth transonic flow and a supersonic-supersonic shock flow for a large relaxation time parameter. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the asymptotic stability of the stationary solution to the outflow problem for the compressible Navier–Stokes–Poisson system in a half line. We show the existence of the stationary solution with the aid of the stable manifold theory. The time asymptotic stability of the stationary solution is obtained by the elementary energy method. Furthermore, for the supersonic flow at spatial infinity, we also obtain an algebraic and an exponential decay rate, when the initial perturbation belongs to the corresponding weighted Sobolev space. The proof is based on a time and space weighted energy method. [ABSTRACT FROM AUTHOR]

A short-rod-shaped moderately halophilic bacterium, designated CUG 00002, was isolated from the sediment of Xiaochaidan salt lake in Qinghai Province, China by using R2A medium. The cells were Gram-staining negative, aerobic, forming creamy and circular colonies with diameters of 2-3 mm on R2A agar when incubated at 30 °C for 3 days. 16S rRNA gene-based phylogenetic analysis indicated that strain CUG 00002 belonged to the genus Halomonas in the class Gammaproteobacteria, showing highest sequence similarity of 97.1 and 96.7 % to Halomonas mongoliensis Z-7009 (=DSM 17332=VKM B2353) and Halomonas shengliensis SL014B-85 (=CGMCC 1.6444=LMG 23897), respectively. The predominant isoprenoid quinone was ubiquinone-9 (Q9), and the major fatty acids were C, summed feature 3 (comprising C ω7c and/or C ω6c) and summed feature 8 (comprising C ω7c or C ω6c). The genomic DNA G+C content of strain CUG 00002 was 61.8 mol%. The above characteristics were consistent with the placement of the organism in the genus Halomonas. The level of DNA-DNA relatedness between CUG 00002 and its most closely related strain H. mongoliensis Z-7009 was 41.0 ± 1.6 %. Based on the results of phenotypic, phylogenetic and biochemical analyses, strain CUG 00002 represents a novel species of the genus Halomonas, for which the name Halomonas xiaochaidanensis sp. nov. is proposed. The type strain is CUG 00002 (=CCTCC AB 2014152=KCTC 42685). [ABSTRACT FROM AUTHOR]

Magnetosomes intracellularly biomineralized by Magnetotactic bacteria (MTB) are membrane-enveloped nanoparticles of the magnetic minerals magnetite (Fe 3 O 4) or greigite (Fe 3 S 4). MTB thrive in oxic-anoxic interface and exhibit magnetotaxis due to the presence of magnetosomes. Because of the unique characteristic and bionavigation inspiration of magnetosomes, MTB has been a subject of study focused on by biologists, medical pharmacologists, geologists, and physicists since the discovery. We herein first briefly review the features of MTB and magnetosomes. The recent insights into the process and mechanism for magnetosome biomineralization including iron uptake, magnetosome membrane invagination, iron mineralization and magnetosome chain assembly are summarized in detail. Additionally, the current research progress in biotechnological applications of magnetosomes is also elucidated, such as drug delivery, MRI image contrast, magnetic hyperthermia, wastewater treatment, and cell separation. This review would expand our understanding of biomineralization and biotechnological applications of bacterial magnetosomes. [Display omitted] • General feature of magnetotactic bacteria and magnetosomes are reviewed. • Magnetosome mineralization processes and mechanism are proposed in detail. • Magnetosomes appear extensive applications in biomedicine and environment. • The prospects for future studies of bacterial magnetosomes were discussed. [ABSTRACT FROM AUTHOR]

An aerobic, orange-pigmented, Gram-negative, coccoid bacterium, named CUG 00006, was isolated from the sediment of Gahai Lake, Qinghai Province, China. This organism was alkaline and grew optimally at pH 9 and 20 °C in the presence of 4 % (w/v) NaCl. Strain CUG 00006 contained Q-10 as the major isoprenoid quinone and C as the main fatty acids. The DNA G + C content was 67.8 mol%. The analysis of 16S rRNA gene sequences indicated that strain CUG 00006 was phylogenetically related to members of the genus Paracoccus, with the similarities ranging from 93.5 to 97.9 %. In particular, strain CUG 00006 was closely related to P. marcusii DSM 11574 (97.7 %), P. haeundaensis KCCM 10460 (97.8 %), and P. carotinifaciens IFO 16121 (97.7 %). On the basis of phylogenetic, physiological, and biochemical characterization, strain CUG 00006 is described as a new species of the genus Paracoccus, for which the name Paracoccus gahaiensis sp. nov. is proposed. The type strain is strain CUG 00006 (=CCTCC M 2014217 = KCTC 42687). [ABSTRACT FROM AUTHOR]

To investigate the effects of relative air humidity (AH) on ‘Fuji’ apple ( Malus domestica Borkh.) peel phenolic compounds and pigment coloration, the bagged fruits were bags moved and then exposed to high AH and low AH conditions, respectively. Cyanidin-3-galactoside, the main anthocyanin compound in apple, and 17 other types of phenolic compounds were detected and their concentrations were also compared between high and low AH treated apple peels. We observed that the removal of bags and subsequent re-exposure to sunlight could significantly decrease the concentrations of syringic acid, caffeic acid, ρ-coumaric acid, and quercetin-3-rhamnoside, but increase the concentrations of ferulic acid, quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rutinoside, and cyanidin-3-galactoside. Furthermore, high AH samples had higher concentrations of chlorogenic acid, ferulic acid, epicatechin, quercetin-3-rutinoside, and cyanidin-3-galactoside than low AH samples as they were in the similar temperature conditions. These results suggested that high AH conditions could significantly improve coloration and the eating quality of fruits. [ABSTRACT FROM AUTHOR]

Poly ( ADP) ribose polymerase ( PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer ( SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single-agent cytotoxicity but selectively potentiated (≥50% reduction in IC50) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin ( CC = 0.672; P = 0.048) and DNA- PKcs protein modulation. Gene expression profiling identified differential expression of a 5-gene panel ( GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell-specific manner. This potentiation correlates with platinum sensitivity, DNA- PKcs expression and a 5-gene expression profile. [ABSTRACT FROM AUTHOR]

For unipolar hydrodynamic model of semiconductor device represented by Euler-Poisson equations, when the doping profile is supersonic, and the boundary data are in subsonic region and supersonic region separately, the system possesses the shock transonic steady-states and the smooth transonic steady-states. In this paper we study the nonlinear structural stability and the linear dynamic instability of these steady transonic solutions. For any relaxation time: 0 < τ ≤ + ∞ , by means of elaborate singularity analysis, we first investigate the structural stability of the C 1 -smooth transonic steady-states, once the perturbations of the initial data and the doping profiles are small enough. We note that, when the C 1 -smooth transonic steady-states pass through the sonic line, they produce singularities for the system, and cause some essential difficulty in the proof of structural stability. Moreover, when the relaxation time is large enough τ ≫ 1 , under the condition that the electric field is positive at the shock location, we prove that the transonic shock steady-states are structurally stable with respect to small perturbations of the supersonic doping profile. Furthermore, we show the linearly dynamic instability for these transonic shock steady-states provided that the electric field is suitable negative. The proofs for the structural stability results are based on singularity analysis, a monotonicity argument on the shock position and the downstream density, and the stability analysis of supersonic and subsonic solutions. The linear dynamic instability of the steady transonic shock for Euler-Poisson equations can be transformed to the ill-posedness of a free boundary problem for the Klein-Gordon equation. By using a nontrivial transformation and the shooting method, we prove that the linearized problem has a transonic shock solution with exponential growths. These results enrich and develop the existing studies. [ABSTRACT FROM AUTHOR]

Abstract: La(PO3)3–Ca(PO3)2 meta-phosphate glass–ceramic composites were prepared by quenching from the melt, followed by heating at 800°C for 20h, in air. Microstructural characterization showed that exposure to water vapor pressures equal to or in excess of 4.2kPa at as low as 550°C resulted in the disproportionation of the lanthanum metaphosphates, with formation of some LaPO4. This reaction puts important limitations on the conditions under which the lanthanum metaphosphates could be used as electrolytes in electrochemical devices. The conductivities at uniform air/water partial pressures around 3kPa, were independent of the water partial pressures used. Comparison of the total ionic effective transference numbers and the proton effective transference number suggested that electronic transport contributed on the average about 7% to the total conductivity in the examined temperature range. The measurements suggested that oxygen ions also participate. The H/D isotope effect, assessed from the ratio σ H 2 O /σ D 2 O ranged from 1.28 at 400°C to 1.35 at 500°C, evidencing dominant proton conduction. At 550°C, the proton effective transference numbers, t H + , determined from the OCVs of cells with oxidizing differential atmospheres were around 0.87, in good agreement with the value derived from the σ H 2 O /σ D 2 O conductivity ratio at 550°C. However, at lower temperatures such agreement was not found. [Copyright &y& Elsevier]

Abstract: In this paper, the compressible non-isentropic Navier–Stokes–Poisson (NSP) system is considered in and the influences of internal electric field on the qualitative behaviors of solutions are analyzed. We observe that the electric field leads to the rotating phenomena in charge transport and reduces the speed of fluid motion, but it does not influence the transport of charge density and the heat diffusion. Indeed, we show that both density and temperature of the NSP system converge to their equilibrium state at the same rate as the non-isentropic compressible Navier–Stokes system, but the momentum decays at the rate , which is slower than the rate for the pure compressible Navier–Stokes system. These convergence rates are also shown to be optimal for the non-isentropic compressible NSP system. [Copyright &y& Elsevier]

Abstract: We report a TEM microstructural and compositional study of proton-conducting (La,Ca)P3O9 (Al-free) and (La,Ca,Al)P3O9 (Al-containing) glass-ceramics, prepared by the crystallization of quenched glass melts. Bright-field Transmission Electron Microscopy imaging, annular dark-field Scanning Transmission Electron Microscopy, and energy dispersive x-ray compositional analysis were used to characterize the structure and chemistry of the glass and crystalline phases of the samples that developed following the treatments at various temperatures, heating-rate and dwell-time. TEM chemical characterization revealed that the crystallized domains were mainly Ca-doped LaP3O9, while the remaining phase was a Ca-rich phosphate glass. Crystallization improved conductivity first (up to a conductivity of nearly 10−4.5 S/cm at 550°C in air). However, the conductivity dropped when the samples were treated at higher temperature or for longer dwell-times, due to a continued Ca-departure from the La-rich crystalline into glass phase. Possible proton transfer mechanisms and strategy to improve conductivity in this doped rare earth metaphosphate glass-ceramic are discussed. [Copyright &y& Elsevier]

Abstract: Al2O3 was added to a 2CaO–La2O3–5P2O5 metaphosphate, to replace 10% of the Ca2+ ions by Al3+, forming a phosphate with the nominal composition 1.8CaO–0.1Al2O3–La2O3–5P2O5. The effect of Al2O3 addition and heat treatment on the microstructure and conductivity of the resulting glass–ceramics was investigated by XRD, SEM, TEM, and AC impedance spectroscopy. Upon transformation from glass to glass–ceramic, conductivities increased significantly. The glasses were isochronally transformed at 700 and at 800 °C for 1 h or 5 h, in air, following heating at 3 or 10 °C/min. With Al2O3 addition, after a heat treatment at 700 °C, 100–300 nm nano-domains of LaP3O9 crystallized from the glass matrix. Annealing at 800 °C produced a further order of magnitude conductivity increase for the Al-free glass, but less so for the Al-containing glass. [Copyright &y& Elsevier]

Abstract: The global in-time semiclassical and relaxation limits of the bipolar quantum hydrodynamic model for semiconductors are investigated in . We prove that the unique strong solution exists and converges globally in time to the strong solution of classical bipolar hydrodynamical equation in the process of semiclassical limit and that of the classical drift–diffusion system under the combined relaxation and semiclassical limits. [Copyright &y& Elsevier]

The initial value problem is considered in the present paper for the bipolar quantum hydrodynamic (QHD) model for semiconductors in ℝ3. The unique strong solution exists globally in time and tends to the asymptotical state with an algebraic decay rate as time goes to infinity is proved. And, the global solution of linearized bipolar QHD system decays in time at an algebraic decay rate from both above and below is shown. This means that in general we cannot get an exponential time-decay rate for bipolar QHD system, which is different from the case of unipolar QHD model (where global solutions tend to the equilibrium state at an exponential time-decay rate) and is mainly caused by the nonlinear coupling and cancelation between two carriers. Moreover, it is also shown that the nonlinear dispersion does not affect the long time asymptotic behavior, which by product gives rise to the algebraic time-decay rate of the solution of the bipolar hydrodynamical model in the semiclassical limit. [ABSTRACT FROM AUTHOR]

Abstract: A dual phase glass–ceramic composite is produced by heating a CaLa(PO3)5 glass at 800 °C for 20 h. The glass–ceramic consists of intertwined crystalline La(PO3)3 and amorphous Ca(PO3)2 with an overall conductivity of 1.52×10−5 S/cm−1 at 550 °C in humidified air. For the water vapor treated glass, the vibration modes of the incorporated water, as well as of P–OH groups, are detected by infrared spectroscopy in the range 3440–1660 cm−1. The conductivity of the glass–ceramic is higher in humidified air than in dry air, consistent with proton conduction. [Copyright &y& Elsevier]

Abstract: In this paper we establish the existence of a unique thermal equilibrium solution of the bipolar multidimensional quantum Euler–Poisson system over the whole space and obtain the relevant semiclassical limit and a combined Planck–Debye length limit through using energy estimating methods and a fixed point theory. [Copyright &y& Elsevier]

This paper concerns the stationary subsonic or sonic–subsonic solution of the electric potential driven problem to the isentropic hydrodynamic model for semiconductors. We give a necessary and sufficient condition to ensure the existence of this kind of solution. Specifically, there exists a subsonic or sonic–subsonic solution to this problem if and only if 0 ≤ ϕ r ≤ ϕ ̄ , with the number ϕ ̄ = O 1 τ . Here, ϕ r is the right side electric potential and τ is the relaxation time. Moreover, there is a number ϕ ̃ ∈ (0 , ϕ ̄ ] such that when ϕ r = ϕ ̃ , there exists a sonic–subsonic solution. In this way, we show the influence of the relationship between the boundary value of the electric potential and the semiconductor effect on the existence of this kind of solution. Finally, we prove the uniqueness of subsonic solution by the energy method under the assumption that ϕ r and ϕ r τ are both small enough. [ABSTRACT FROM AUTHOR]

A magnetosome-producing bacterium Acidithiobacillus ferrooxidans BYM (At. ferrooxidans BYM) was isolated and magnetically screened. The magnetosome yield from 0.5896 to 13.1291 mg/g was achieved under different aeration rates, ferrous sulfate, ammonium sulfate, and gluconic acid concentrations at 30 ℃. TEM observed 6–9 magnetosomes in size of 20–80 nm irregularly dispersed in a cell. STEM-EDXS and HRTEM-FFT implied that the elongated-prismatic magnetite magnetosomes with {110} crystal faces grown along the [111] direction. Whole-genome sequencing and annotation of BYM showed that 3.2 Mb chromosome and 47.11 kb plasmid coexisted, and 322 genes associated with iron metabolism were discovered. Ten genes shared high similarity with magnetosome genes were predicted, providing sufficient evidence for the magnetosome-producing potential of BYM. Accordingly, we first proposed a hypothetic model of magnetosome formation including vesicle formation, iron uptake and mineralization, and magnetite crystal maturation in At. ferrooxidans. These indicated that At. ferrooxidans BYM would be used as a commercial magnetosome-producing microorganism. [ABSTRACT FROM AUTHOR]

The doxorubicin (DOX) was successfully coupled to the magnetosomes from Acidithiobacillus ferrooxidans (At. ferrooxidans) by genipin bridging. The parameters (magnetosome concentration, DOX concentration, genipin concentration-, and cross-link time) expected for temperature significantly influenced the coupling rate. Bacterial magnetosome-doxorubicin complexes (BMDCs) were characterized by transmission electron microscope (TEM), particle size analyzer and Fourier transform infrared spectroscopy. Results indicated that BMDCs exhibited a mean particle size of 83.98 mm and displayed a negative charge. The chemical reaction occurring between CO and NH group and the physical adsorption predominated by electrostatic interaction were found to involve in coupling. BMDCs can release 40% of DOX in simulated gastrointestinal conditions within 38 h. Kinetic models including Higuchi, Korsmeyer–Peppas, Zero order, First order, Hixon-Crowell, Baker-Lonsdale, and Weibull and Gompertz were utilized to explore the release mechanism of DOX from BMDCs. All models were found to fit well (r2 ≥ 0.8144) with the release data and the Gompertz was the best fit model (r2 = 0.9742), implying that the complex mechanisms involving Fickian and Gompertz diffusion contributed to the release. These findings suggested that magnetosomes from At. ferrooxidans have great potential applications in biomedical and clinical fields as the carrier of target drug delivery systems in the future. [ABSTRACT FROM AUTHOR]

In this paper, we study the well-posedness, ill-posedness and uniqueness of the stationary 3-D radial solution to the bipolar isothermal hydrodynamic model for semiconductors. The density of electron is imposed with sonic boundary and interiorly subsonic case and the density of hole is fully subsonic case. It is difficult to estimate the upper and lower bounds of the holes due to the coupling of electrons and holes and the degeneracy of electrons at the boundary. Thus, we use the topological degree method to prove the well-posedness of solution. We prove the ill-posedness of subsonic solution under some conditions by direct mathematical analysis and contradiction method. The ill-posedness property shows significant difference to the unipolar model. Another highlight of this paper is the application of specific energy method to obtain the uniqueness of solution in two cases. One case is the relaxation time τ = ∞ , namely, the pure Euler-Poisson case; the other case is j τ ≪ 1 , which means that, when the current flow is sufficiently small and the relaxation time is sufficiently large both can satisfy. [ABSTRACT FROM AUTHOR]

• ACK1 inhibition synergizes with osimertinib against EGFR mutant NSCLC cells. • ACK1 inhibition delays emergence of osimertinib resistance in vitro and in vivo. • Targeting ACK1 restores the response of osimertinib-resistant cells to osimertinib. • Targeting ACK1 as a novel strategy to delay and overcome osimertinib resistance. The emergence of acquired resistance to the third generation EGFR inhibitor, osimertinib (AZD9291 or TAGRISSO™), is an unavoidable huge clinical challenge. The involvement of ACK1, a non-receptor tyrosine kinase with an oncogenic function, in regulating cell response to osimertinib has not been investigated and thus is the focus of this study. Drug effects on cell growth were evaluated by measuring cell numbers and colony formation. Apoptosis was monitored with flow cytometry for annexin V-positive cells and Western blotting for protein cleavage. Intracellular protein and mRNA alterations were detected with Western blotting and qRT-PCR, respectively. Drug effects on delaying osimertinib acquired resistance were determined using colony formation in vitro and xenografts in nude mice in vivo, respectively. Cell senescence was assayed by β-galactosidase staining. Inhibition of ACK1 with the novel ACK1 inhibitor, (R)- 9b synergized with osimertinib in inhibiting the growth of EGFR mutant NSCLC cell lines. Similar results were also generated with ACK1 gene knockdown. The combination of osimertinib and (R)- 9b enhanced induction of apoptosis. In both in vitro and in vivo long-term resistance delay assays, the combination of (R)- 9b and osimertinib clearly delayed the emergence of osimertinib-resistance. Further, the (R)- 9b and osimertinib combination was also effective in inhibiting the growth of EGFR mutant NSCLC cell lines with acquired resistance to osimertinib, which possess elevated levels of ACK1, and the growth of osimertinib-resistant tumors in vivo. In some resistant cell lines, the combinations induced senescence in addition to induction of apoptosis. These novel findings suggest that ACK1 inhibition might be a potential and innovative strategy for delaying and overcoming osimertinb acquired resistance. [ABSTRACT FROM AUTHOR]

As shown in [17,18] , for the hydrodynamic model of semiconductors represented by Euler-Poisson equations with sonic boundary and subsonic/supersonic doping profile, the structure of stationary solutions are very complicated. It may possess various solutions like subsonic/supersonic/transonic flows. In this paper, we consider a more challenging case where the doping profile is transonic, which is categorized into two types: subsonic-dominated and supersonic-dominated. In the subsonic-dominated case, we show that the system has a unique interior subsonic solution, at least one interior supersonic solution and infinitely many transonic solutions under the suitable assumptions. However, the difference with the case of subsonic doping profile is that the interior subsonic solution and interior supersonic solution may not exist in special cases when the relaxation time is small. In the supersonic-dominated case, the non-existence and existence of all types of solutions are also obtained. The approach adopted is the technical compactness analysis combining the Green's function method. Here, the results obtained perfectly develop the existing studies. [ABSTRACT FROM AUTHOR]

Fluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and normal human colon epithelial cells. In vivo animal models were used to document the antitumor activity of HQ and baicalin. The mechanism of growth inhibitory activity of HQ is due to inhibition of proliferative signaling pathways including the CDK-RB pathway. In addition, HQ enhanced the antitumor effects of 5-FU and capecitabine in vivo. Furthermore, we identified baicalin as an active component of HQ. The combination of baicalin and 5-FU demonstrated synergistic activity against 5-FU-resistant RKO-R10 cells. The combination significantly inhibited in vivo tumor growth greater than each treatment alone. RPPA results showed that the signaling pathway alterations in CRC cells were similar following HQ and baicalin treatment. Together, these results indicate that HQ and its component baicalin enhance the effect of 5-fluorouracil-based chemotherapy via inhibition of CDK-RB pathway. These findings may provide the rational basis for developing agents that can overcome the development of cellular drug resistance. 9Q3bw5kPrTjBvtYuEHSNma Video Abstract [ABSTRACT FROM AUTHOR]

An abstract of the article "Halomonas Erhaiensis sp. nov., a Moderately Halotolerant Bacterium Isolated from Erhai Lake, Qinghai Province, China," by Zhang Guojing and colleagues is presented.

The 3rd generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs; e.g., AZD9291), which selectively and irreversibly inhibit EGFR activating and T790M mutants, represent very promising therapeutic options for patients with non-small cell lung cancer (NSCLC) that has become resistant to 1st generation EGFR-TKIs due to T790M mutation. However, eventual resistance to the 3rd generation EGFR-TKIs has already been described in the clinic, resulting in disease progression. Therefore, there is a great challenge and urgent need to understand how this resistance occurs and to develop effective strategies to delay or overcome the resistance. The current study has demonstrated that Met amplification and hyperactivation is a resistance mechanism to both 1st and 3rd generation EGFR-TKIs since both erlotinib- and AZD9291-resistant HCC827 cell lines possessed amplified Met gene and hyperactivated Met, and were cross-resistant to AZD9291 or erlotinib. Met inhibition overcame the resistance of these cell lines to AZD9291 both in vitro and in vivo, including enhancement of apoptosis or G1 cell cycle arrest. Hence, we suggest that Met inhibition is also an effective strategy to overcome resistance of certain EGFR-mutated NSCLCs with Met amplification to AZD9291, warranting the further clinical validation of our findings. [ABSTRACT FROM AUTHOR]

Human non-small cell lung cancer (NSCLC) displays activated MEK/ERK signaling due to a high frequency of K-Ras mutation and is thus a potential candidate for MEK-targeted therapy. The current study focuses on demonstrating the activity of MEK162 (binimetinib), a MEK inhibitor under clinical testing, against NSCLC and exploring possible mechanism-driven strategies to enhance its therapeutic efficacy. MEK162 inhibits the growth of human NSCLC cell lines with varied potencies through induction of G1 cell cycle arrest and apoptosis. Moreover, it induces autophagy and accordingly the combination of MEK162 with the autophagy inhibitor, chloroquine, synergistically inhibits the growth of NSCLC cells and enhances apoptosis. MEK162 activates Akt signaling while effectively inhibiting MEK/ERK signaling. Accordingly, the combination of MEK162 and BKM120 (buparlisib), a pan-PI3K inhibitor, abrogates induced Akt activation and significantly augments therapeutic efficacy against the growth of NSCLC cells both in vitro and in vivo . Hence our findings warrant further evaluation of these rational combinations in the clinic. [ABSTRACT FROM AUTHOR]

Abstract: This paper proposes a new node centrality measurement in a weighted network, the communication centrality, which is inspired by Hirsch’s -index. We investigated the properties of the communication centrality, and proved that the distribution of the communication centrality has the power-law upper tail in weighted scale-free networks. Relevant measures for node and network are discussed as extensions. A case study of a scientific collaboration network indicates that the communication centrality is different from other common centrality measures and other -type indexes. Communication centrality displays moderate correlation with other indexes, and contains a well-balanced mix of other centrality measures and cannot be replaced by any of them. [Copyright &y& Elsevier]

Strong inflammatory indicators such as C-reactive protein (CRP), high-sensitivity CRP (hsCRP), and hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT), and red blood cell distribution width (RDW), may be related with contrast-induced nephropathy (CIN). Our meta-analysis aimed at exploring the relationship between these indicators and CIN incidence among patients undergoing coronary intervention. Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and Science Direct from their inception to June 3, 2020. Meta-analysis was performed on pooled eligible studies. Finally, 26 studies involving 29 454 patients were included. Pooled analysis revealed that patients with higher CRP (odds ratio [OR] = 1.06, 95% CI: 1.01-1.12, P =.02), hsCRP (OR = 1.03, 95% CI: 1.01-1.06, P =.004), NLR (OR = 1.11, 95% CI: 1.01-1.20, P =.02), RDW (OR = 1.35, 95% CI: 1.19-1.53, P <.001), and lower HCT (OR = 0.94, 95% CI: 0.92-0.97, P =.003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR = 1.12, 95% CI: 0.99-1.26, P =.07). Pre-angiography CRP/hsCRP and some hematological indices are associated with CIN. [ABSTRACT FROM AUTHOR]

Background: The majority of patients with non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations respond well to osimertinib (AZD9291), a third-generation, mutation-selective EGFR inhibitor. The current study focuses on determining whether targeting MEK/ERK signaling prevents or delays the development of acquired resistance to osimertinib.Methods: Drug effects on cell survival were determined by measuring cell number alterations. Apoptosis was assessed with flow cytometry for the detection of annexin V-positive cells and with Western blotting for protein cleavage. Alterations of proteins in cells were detected with Western blotting. Drug effects on delaying the emergence of osimertinib resistance were evaluated with colony formation in vitro and xenografts in nude mice in vivo.Results: Osimertinib combined with an MEK or ERK inhibitor synergistically decreased cell survival with enhanced induction of apoptosis in EGFR-mutant NSCLC cells but not in EGFR wild-type NSCLC cells. These combinations were also very effective in killing cell clones with primary intrinsic resistance to osimertinib. Continuous and intermittent pharmacologic inhibition of MEK/ERK signaling delayed the emergence of osimertinib resistance both in vitro and in vivo.Conclusions: These results provide strong preclinical evidence in support of targeting MEK/ERK signaling as a strategy for delaying or preventing acquired resistance to osimertinib in the clinic to improve the long-term therapeutic efficacy of osimertinib. From a clinical standpoint, the data support the evaluation of an intermittent treatment schedule of osimertinib in combination with an MEK or ERK inhibitor in patients with EGFR-mutated NSCLC. [ABSTRACT FROM AUTHOR]

Sunlight radiation is a main environmental factor which affects anthocyanin synthesis. To clarify the regulatory mechanism of sunlight on the synthesis of anthocyanin in apple peel, bagged apples were exposed to diverse intensities of sunlight through different shading treatments. Under an increased solar ultraviolet-B (UV-B) light intensity, the concentration of anthocyanin in apple peels was consistent with the Michaelis–Menten equation. Under lower sunlight intensities, diphenyleneiodonium chloride (DPI, an inhibitor of plasma membrane NAD(P)H oxidase) treatment increased both the concentration of cyanidin-3-glycoside and the activity of dihydroflavonol 4-reductase (DFR). However, under higher sunlight intensities, DPI treatment decreased the concentrations of cyanidin-3-glycoside and quercetin-3-glycoside, as well as the activities of DFR and UDP-glycose: flavonoid 3-O-glycosyltransferase (UFGT). These results indicate that, under low sunlight intensity, anthocyanin synthesis in apple peel was limited by the supply of the substrate cyanidin, which was regulated by the DFR activity. Nevertheless, after exposure to high sunlight intensity, the anthocyanin produced in the apple peel was dependent on UFGT activity. [ABSTRACT FROM AUTHOR]

Identifying important nodes is crucial for understanding network structure and function in the research of network science. A variety of methods are proposed to evaluate different quality aspects of node's importance, in most cases ignoring the directed nature of links. In this paper, we introduce the bi-directional h-index to measure node's importance, and the bi-directional k -core (B-core) decomposition for partition of network and detection dense subgraphs in directed networks. Considering the direction of links in directed networks, the bi-directional h-index and B-core decomposition can reflect the mutual influence of two kinds of reverse relations. By B-core decomposition, each node is assigned a bi-directional coreness to express its importance. The bi-directional h-index uses h-index algorithm for iterative calculation, and the directed degree centrality is its initial value, we prove that bi-directional coreness is its stable value. When the network is undirected, the bi-directional h-index is equivalent to the node's h-index, and the B-core decomposition is equivalent to the classic graph-theoretic notion of k -core decomposition. Finally, we show the computation and convergence of bi-directional h-index and its difference from other methods in ranking of node's importance in a real-world directed network. • Bi-directional h-index for node' importance is proposed in directed networks. • B-core decomposition for partition of network and detection of dense subgraphs is proposed in directed networks. • Bi-directional coreness is the stable value of bi-directional h-index. • We establish a larger conceptual framework and some existing methods are included. [ABSTRACT FROM AUTHOR]

N -alkane-based proxies are widely employed to reconstruct paleoclimate and paleoenvironment in lacustrine environments. However, little is known about the influence of microbially mediated alkane-degradation on n -alkane-derived proxies. In this study, the chemical composition of n -alkanes and microbially mediated n -alkane degradation potential were investigated in the surface sediment samples collected from seven lakes with a range of salinity from freshwater to salt saturation on the northern Qinghai-Tibetan Plateau (QTP). The results showed that the chemical composition of n -alkanes differed among the studied QTP lakes. Significant correlations were observed between salinity and some n -alkane-based paleoclimate and paleoenvironment proxies, such as ratio of C 21 −/C 22 +, average chain length (ACL) and carbon preference index (CPI). This suggested that salinity may affect the validity of some n -alkane-based paleoclimate and paleoenvironment proxies. Alkane-degrading bacteria were abundant and widespread in the studied freshwater and saline/hypersaline lakes but were minor or absent in salt-saturation lakes. The obtained alkane-degrading bacterial strains showed active ability to degrade n -hexadecane. This suggested that the salinity influence on the n -alkane distribution may be partially related to microbial degradation, which awaits further in-situ investigation. So salinity variation should be taken into account when using n -alkane-based proxies for reconstructing paleoclimate and paleoenvironment in lakes. • Chemical composition of n -alkanes differed among the studied lakes of different salinity • Salinity may affect the validity of n -alkane-based paleoclimate proxies. • Alkane-degrading bacteria showed active ability to degrade n -hexadecane. • Microbial degradation may partially account for salinity influence on n -alkane distribution. • Salinity variation should be taken into account when using n -alkane-based proxies. [ABSTRACT FROM AUTHOR]

In this paper, the problem of ranking multi-dimensional uncertain information based on fuzzy order is studied. At first, a specific fuzzy order on the fuzzy ellipsoid number space is defined, with which we can set up a dynamic ranking method which changes with the change of the level r for some objects which can be characterized by some multichannel uncertain digital information. Then its properties are investigated, some related results are obtained. And then, we give a practical example to show how to set up a dynamic ranking method which changes with the change of the level r for some objects which can be characterized by some multichannel uncertain digital information by using the fuzzy order proposed by us in the paper. [ABSTRACT FROM AUTHOR]

Highlights • CD40 × HER2 ScDb fragment was constructed by SOE-PCR and expressed using a prokaryotic expression system. • CD40 × HER2 ScDb could inhibit the proliferation of tumor cells by stimulating tumor-specific immunoreactions in vivo and vitro experiments. • CD40 × HER2 ScDb could inhibit the proliferation of tumor cells by blocking the HER2-related signaling pathway. Abstract Our aim was to construct a CD40×HER2 single chain diabody (ScDb) and determine its tumor-specific immune activation and anti-HER2 function. Overlap extension-polymerase chain reaction was applied in the construction of ScDb, and the protein was expressed with the pET28a (+)-Rosetta prokaryotic expression system. Soluble ScDb was purified by a nickel-nitrilotriacetic acid column. Dendritic cells (DC) was stimulated by ScDb and inhibited 4T1 cells proliferation in vitro. In 4T1 tumor mice model, lymphocyte infiltration was prominently detected in ScDb group, Caspase-3 expression was significantly upregulated. ScDb was labeled using quantum dots. Immunofluorescence assay indicated ScDb exhibited high affinity to HER2. T6-17 cells were inhibited by ScDb in vitro. The phosphorylation and expression levels of AKT, ERK were markedly decreased. In T6-17 tumor mice model. Compared to CD40 ScFv, HER2 ScFv and normal saline groups, tumor volume diminished significantly in ScDb group, and tumor cells showed extensive deformation, and pervasive karyopyknosis and karyorrhexis were found. In the present study, we successfully constructed a ScDb fragment and expressed it using a prokaryotic expression system. The in vivo and in vitro experimental results indicated that ScDb could inhibit the proliferation of tumor cells by stimulating the tumor-specific immunoreaction and blocking the HER2-related signaling pathway. [ABSTRACT FROM AUTHOR]

The initial boundary value problem for the compressible barotropic Navier–Stokes equations is investigated in the case that the initial density has a jump discontinuity across an interior closed curve in two-dimensional bounded domain. If the initial data is a small perturbation of the constant state and the interior closed curve is near a circle inside the domain, the global existence and large time behavior of the piecewise strong solution is shown, in particular, the jump of the fluid density across the convecting curve decays exponentially in time. [ABSTRACT FROM AUTHOR]

Summary Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is “hijacked” to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers. The resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity, leading to increased PDC flux and oxidative phosphorylation with attenuated cancer cell proliferation and tumor growth. These findings provide a mechanistic understanding of how oncogenic events signal through distinct acetyltransferases to regulate cancer metabolism and suggest ACAT1 as an anti-cancer target. [ABSTRACT FROM AUTHOR]

Background: SCLC has limited treatment options and inadequate preclinical models. Promising activity of arsenic trioxide (ASO) recorded in conventional preclinical models of SCLC supported the clinical evaluation of ASO in patients. We assessed the efficacy of ASO in relapsed SCLC patients and in corresponding patient-derived xenografts (PDX).Methods: Single arm, Simon 2-stage, phase II trial to enroll patients with relapsed SCLC who have failed at least one line of therapy. ASO was administered as an intravenous infusion over 1-2 h daily for 4 days in week 1 and for 2 days in weeks 2-6 of an 8-week cycle. Treatment continued until disease progression. Pretreatment tumor biopsy was employed for PDX generation through direct implantation into subcutaneous pockets of SCID mice without in vitro manipulation and serially propagated for five generations. Ex vivo efficacy of cisplatin (3 mg/kg i.p. weekly) and ASO (3.75 mg/kg i.p. every other day) was tested in PDX representative of platinum sensitive and platinum refractory SCLC.Results: The best response in 17 evaluable patients was stable disease in 2 (12 %), progressive disease in 15 (88 %) patients and median time-to-progression of seven (range 1-7) weeks. PDX was successfully grown in 5 of 9 (56 %) transplanted biopsy samples. Serially-propagated PDXs preserved characteristic small cell histology and genomic stability confirmed by immunohistochemistry, short tandem repeat (STR) profiling and targeted sequencing. ASO showed in vitro cytotoxicity but lacked in vivo efficacy against SCLC PDX tumor growth.Conclusions: Cisplatin inhibited growth of PDX derived from platinum-sensitive SCLC but was ineffective against PDX from platinum-refractory SCLC. Strong concordance between clinical and ex vivo effects of ASO and cisplatin in SCLC supports the use of PDX models to prescreen promising anticancer agents prior to clinical testing in SCLC patients. Trial Registration The study was registered at http://www.clinicaltrials.gov (NCT01470248). [ABSTRACT FROM AUTHOR]

Summary The BH4 domain of Bcl2 is required for its antiapoptotic function, thus constituting a promising anticancer target. We identified a small-molecule Bcl2-BH4 domain antagonist, BDA-366, that binds BH4 with high affinity and selectivity. BDA-366-Bcl2 binding induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer xenografts derived from cell lines and patient without significant normal tissue toxicity at effective doses. mTOR inhibition upregulates Bcl2 in lung cancer cells and tumor tissues from clinical trial patients. Combined BDA-366 and RAD001 treatment exhibits strong synergy against lung cancer in vivo. Development of this Bcl2-BH4 antagonist may provide a strategy to improve lung cancer outcome. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we present the latest results on developing and integrating extreme ultraviolet lithography (EUVL) at Intel. The world’s first commercial EUV exposure tool was installed in Intel’s development fab, linked to a resist track, and had successfully demonstrated key tool specifications by the end of 2004. Exercising this micro-exposure tool (MET) is a significant step in the path toward inserting EUVL into high-volume manufacturing. Full patterning development of the small features required for the 32nm node are enabled by coupling the high-resolution printing capability of the MET with a state-of-the-art wafer fabrication facility. Moreover, using the MET in a fab environment assists in the identification and resolution of issues associated with the novel aspects of EUVL. We are actively using this tool to study EUV resists, novel processing, and masks. Results of these studies are presented here. Data include imaging performance for both line-space and contact hole patterns on relevant substrates, early etch results, and a mask defect printability study. [Copyright &y& Elsevier]

Summary Platinum-based chemotherapeutics represent a mainstay of cancer therapy, but resistance limits their curative potential. Through a kinome RNAi screen, we identified microtubule-associated serine/threonine kinase 1 (MAST1) as a main driver of cisplatin resistance in human cancers. Mechanistically, cisplatin but no other DNA-damaging agents inhibit the MAPK pathway by dissociating cRaf from MEK1, while MAST1 replaces cRaf to reactivate the MAPK pathway in a cRaf-independent manner. We show clinical evidence that expression of MAST1, both initial and cisplatin-induced, contributes to platinum resistance and worse clinical outcome. Targeting MAST1 with lestaurtinib, a recently identified MAST1 inhibitor, restores cisplatin sensitivity, leading to the synergistic attenuation of cancer cell proliferation and tumor growth in human cancer cells and patient-derived xenograft models. [ABSTRACT FROM AUTHOR]

Summary Loss of LKB1 is associated with increased metastasis and poor prognosis in lung cancer, but the development of targeted agents is in its infancy. Here we report that a glutaminolytic enzyme, glutamate dehydrogenase 1 (GDH1), upregulated upon detachment via pleomorphic adenoma gene 1 (PLAG1), provides anti-anoikis and pro-metastatic signals in LKB1-deficient lung cancer. Mechanistically, the GDH1 product α-KG activates CamKK2 by enhancing its substrate AMPK binding, which contributes to energy production that confers anoikis resistance. The effect of GDH1 on AMPK is evident in LKB1-deficient lung cancer, where AMPK activation predominantly depends on CamKK2. Targeting GDH1 with R162 attenuated tumor metastasis in patient-derived xenograft model and correlation studies in lung cancer patients further validated the clinical relevance of our finding. Our study provides insight into the molecular mechanism by which GDH1-mediated metabolic reprogramming of glutaminolysis mediates lung cancer metastasis and offers a therapeutic strategy for patients with LKB1-deficient lung cancer. [ABSTRACT FROM AUTHOR]

The article discusses the diversity and distribution of T4-like myoviruses in the saline lakes of Qinghai-Tibetan plateau in China. Topics discussed include the bacteriophage distribution in the hypersaline lakes, the microbial community structure, and the dominance of Myoviridae in aquatic ecosystems.