With Ti addition in a NbMoTaW alloy, a new refractory high entropy alloy (HEA) of TiNbMoTaW was developed. It has been found that this HEA possesses single body-centered cubic (BCC) phase structure, ...and could sustain the phase structure even after annealing at 1200 °C for 24 h. In comparison with the mechanical properties of the NbMoTaW and VNbMoTaW HEAs, the room-temperature yield strengths and compressive plastic strains of the TiNbMoTaW and TiVNbMoTaW HEAs are significantly enhanced. In particular, the TiNbMoTaW and TiVNbMoTaW HEAs also show very promising high temperature strength. Their yield strengths are as high as ∼586 and ∼659 MPa at 1200 °C, respectively. The present results indicate that Ti addition is beneficial to the strength and the compressive ductility of the refractory HEAs at room-temperature. It is suggested that the present refractory HEAs possess the potentials in applications of high temperature structure materials.
•The NbMoTaW and VNbMoTaW HEAs possess outstanding mechanical properties at high temperature, while they are brittle at room-temperature, which would limit their broad applications. In the present work, we successfully improve their strengths and the compressive ductility at room-temperature by the alloying method.•It is found that element segregation may contribute to the ductility of the HEAs.•The high-temperature mechanical performance of the TiNbMoTaW and TiVNbMoTaW HEAs makes them to be potential materials for high-temperature applications.
Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in ...patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery.
Gemcitabine metabolites were analysed in
;
;
(KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation.
Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%.
Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.
Abstract
Contemporary ultraintense, short-pulse laser systems provide extremely compact setups for the production of high-flux neutron beams, such as those required for nondestructive probing of ...dense matter, research on neutron-induced damage in fusion devices or laboratory astrophysics studies. Here, by coupling particle-in-cell and Monte Carlo numerical simulations, we examine possible strategies to optimise neutron sources from ion-induced nuclear reactions using 1-PW, 20-fs-class laser systems. To improve the ion acceleration, the laser-irradiated targets are chosen to be ultrathin solid foils, either standing alone or preceded by a plasma layer of near-critical density to enhance the laser focusing. We compare the performance of these single- and double-layer targets, and determine their optimum parameters in terms of energy and angular spectra of the accelerated ions. These are then sent into a converter to generate neutrons via nuclear reactions on beryllium and lead nuclei. Overall, we identify configurations that result in neutron yields as high as
$$\sim 10^{10}\,{\mathrm{n}}\,{\mathrm{sr}}^{-1}$$
∼
10
10
n
sr
-
1
in
$$\sim 1$$
∼
1
-cm-thick converters or instantaneous neutron fluxes above
$$10^{23}\,{\mathrm{n}}\,{\mathrm{cm}}^{-2}\,{\mathrm{s}}^{-1}$$
10
23
n
cm
-
2
s
-
1
at the backside of
$$\lesssim 100$$
≲
100
-
$$\upmu$$
μ
m-thick converters. Considering a realistic repetition rate of one laser shot per minute, the corresponding time-averaged neutron yields are predicted to reach values (
$$\gtrsim 10^7\,{\mathrm{n}} \,{\mathrm{sr}}^{-1}\,{\mathrm{s}}^{-1}$$
≳
10
7
n
sr
-
1
s
-
1
) well above the current experimental record, and this even with a mere thin foil as a primary target. A further increase in the time-averaged yield up to above
$$10^8\,{\mathrm{sr}}^{-1}\,{\mathrm{s}}^{-1}$$
10
8
sr
-
1
s
-
1
is foreseen using double-layer targets.
We investigate the wavepacket dynamics of quasiparticles in a Su–Schrieffer–Heeger lattice with third-nearest-neighbor hopping. The results reveal that the life-span of Zitterbewegung can be ...prolonged. To better understand the mechanism, we discuss the band structure and the long-time average of inverse participation rate. The results show that the band structure can be effectively manipulated as a quasi-flat band by introducing the third-nearest-neighbor hopping. This, as a unique advantage over the standard Su–Schrieffer–Heeger model, will bring about restrained diffusion of the wavepacket as well as dramatically stretched life-span of Zitterbewegung, thus will promise wide applications in condensed matter physics.
To evaluate the refractive outcomes in children treated after intravitreal injection of bevacizumab (IVB) for retinopathy of prematurity (ROP).
A retrospective, bi-centre study of 34 patients (64 ...eyes) was conducted. The patients were divided into three groups, patients received intravitreal IVB (IVB group), patients received combined IVB and laser treatment (IVB + Laser group), or patients received lens-sparing vitrectomy (IVB + LSV group). Cycloplegic refraction and axial length (AXL) were evaluated at 2 years old.
The prevalences of myopia and high myopia were 47.5 and 10.0% in the IVB group, respectively, which were lower than those in the IVB + Laser (82.4 and 29.4%) and IVB + LSV (all 100%) groups (P = 0.001 and P < 0.001). The prevalences of emmetropia in the IVB group, IVB + Laser group, and IVB + LSV group were 50, 5.9, and 0% (P = 0.001). The AXL were similar among all groups.
At the 2-year follow-up, severe ROP patients treated with IVB alone were more likely to remain emmetropic and had lower prevalences of myopia and high myopia. The development of high myopia in severe ROP patients could not be explained by AXL changes but may be associated with abnormalities in the anterior segment.
We assess the limits of predictability of the large‐scale cloud patterns in the boreal winter Madden‐Julian Oscillation (MJO) as measured through outgoing longwave radiation (OLR) alone, a proxy for ...convective activity. A recent advanced nonlinear time series technique, nonlinear Laplacian spectral analysis, is applied to the OLR data to define two spatial modes with high intermittency associated with the boreal winter MJO. A recent data‐driven physics‐constrained low‐order stochastic modeling procedure is applied to these time series. The result is a four‐dimensional nonlinear stochastic model for the two observed OLR variables and two hidden variables involving correlated multiplicative noise defined through energy‐conserving nonlinear interaction. Systematic calibration and prediction experiments show the skillful prediction by these models for 40, 25, and 18 days in strong, moderate, and weak MJO winters, respectively. Furthermore, the ensemble spread is an accurate indicator of forecast uncertainty at long lead times.
Key Points
NLSA is applied to the OLR data to define two spatial modes of boreal winter MJO
Physics‐constrained low‐order stochastic modeling is applied to the two modes
Large‐scale cloud patterns of the boreal winter MJO are skillfully predicted
The importance of oligosaccharides and their conjugates in various biological and pathological processes has stimulated growing interest in the development of (neo)glycoconjugates. Thanks to its high ...nucleophilicity, hydroxylamine has been employed as a powerful chemoselective ligation tool. Great effort has been focused on carbohydrates bearing aminooxy or N-hydroxy amino groups for organic synthesis, glycobiology and drug discovery. This review provides an overview of N-O linked carbohydrates and glycoconjugates, focusing particularly on the synthetic methodologies and chemical and physicochemical properties as well as biological and medical applications of N-glycosyl and O-glycosyl hydroxylamines, N-hydroxy amino and O-amino sugar as well as sugar aminooxy acid derivatives.
Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β (TGF-β) is implicated in hepatocarcinogenesis and hepatocellular carcinoma (HCC) metastasis. HAb18G/CD147, which ...belongs to the CD147 family, is an HCC-associated antigen that has a crucial role in tumor invasion and metastasis. The goal of this study was to investigate the role of HAb18G/CD147 during EMT in hepatocarcinogenesis. Human normal hepatic cell lines QZG and L02, primary mouse hepatocytes and nude mouse models were used to determine the role of HAb18G/CD147 in EMT, and the involvement of the TGF-β-driven pathway. A dual-luciferase reporter assay and ChIP were used to investigate the transcriptional regulation of the CD147 gene. Samples from patients with liver disease were assessed to determine the relationship between HAb18G/CD147 and typical markers for EMT. Our results show that upregulation of HAb18G/CD147 is induced by TGF-β coupled with downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The expression of HAb18G/CD147 is controlled by the cell survival PI3K/Akt/GSK3β signaling pathway, and is directly regulated by the transcription factor Slug. Transfection of CD147 also induces an elevated expression of TGF-β. CD147-transfected hepatocytes have mesenchymal phenotypes that accelerate tumor formation and tumor metastasis in vivo. Immunohistochemistry analysis shows a negative correlation between HAb18G/CD147 and E-cadherin expression (r(s)=-0.3622, P=0.0105), and a positive correlation between HAb18G/CD147 and Slug expression (r(s)=0.3064, P=0.0323) in human HCC tissues. Our study uncovers a novel role of HAb18G/CD147 in mediating EMT in the process of HCC progression and showed that CD147 is a Slug target gene in the signaling cascade TGF-β→PI3K/Akt→GSK3β→Snail→Slug→CD147. Our results suggest that CD147 may be a potential target for the treatment and prevention of HCC.
Improving intrinsic reactivity is one of the key requirements in applying zero-valent iron in the field. As a new kind of zero-valent iron, iron based amorphous alloys were recently found to be ...capable of rapidly remediating wastewater. However, the mechanisms for the rapid degradation have not yet been fully understood. In this study, commercial Fe–Si–B amorphous alloy ribbons (Fe–Si–B AR ) were used to degrade azo dyes (Direct Blue 6 and Orange II) to study the reaction kinetics, pathway and mechanism behind the high reactivity of these iron based amorphous alloys. The results show that, under the same conditions, the surface normalized reaction rate constants for the decomposition of Orange II and Direct Blue 6 by Fe–Si–B AR could be 1300 and 60 times larger respectively than those obtained by using 300 mesh iron powders. Through UV-vis spectrophotometry and mass spectrometry, it is found that the intermediate products of the azo dyes degraded by Fe–Si–B AR are similar to those produced in degradation by iron powders. However, the controlling step of the degradation reaction by Fe–Si–B AR turns out to be the diffusion process rather than the surface chemical reaction found in the reaction by iron powders. Further analysis indicates that the high degradation efficiency of Fe–Si–B AR results from its amorphous structure and the metalloid additions, which could enhance the catalytic effect and promote the formation of a non-compact and easily detached oxide layer on the surface. The experiments under different environmental conditions show that the factors that influence the degradation efficiency of crystalline iron powders affect that of Fe–Si–B AR in a similar way, but Fe–Si–B AR is capable of efficiently degrading wastewater under broader conditions than the crystalline iron powders. The results indicate that Fe–Si–B AR is a promising environmental catalyst for wastewater treatment.
MnO
x
/Al
2
O
3
-P catalyst was synthesized by polyol process and evaluated in catalytic ozonation of toluene in air at room temperature. The effects of polyol synthesis temperature and time were ...optimized using response surface methodology. The performance of the optimized polyol catalyst was compared with a catalyst prepared by the impregnation method (MnO
x
/Al
2
O
3
-I). Polyol catalyst had higher toluene and ozone conversions with less carbon deposition and higher selectivity towards CO
2
in the product than the impregnated catalyst. Nearly 80% of toluene was removed using MnO
x
/Al
2
O
3
-P after 120 min of reaction, which is higher than MnO
x
/Al
2
O
3
-I (70%). Characterization studies showed that MnO
x
/Al
2
O
3
-P has smaller manganese particle size, higher dispersion, and higher surface area than MnO
x
/Al
2
O
3
-I. Both catalysts were mostly composed of Mn
3+
phase, while MnO
x
/Al
2
O
3
-P had a higher amount of Mn
2+
. The higher activity of the polyol catalyst is attributed to smaller manganese particle size, higher catalyst surface area, and lower oxidation state of manganese.
Graphic Abstract
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