The tumor suppressor gene p53 has been implicated in the regulation of epithelial-mesenchymal transition (EMT) and tumor metastasis by regulating microRNA (miRNA) expression. Here, we report that ...mutant p53 exerts oncogenic functions and promotes EMT in endometrial cancer (EC) by directly binding to the promoter of miR-130b (a negative regulator of ZEB1) and inhibiting its transcription. We transduced p53 mutants into p53-null EC cells, profiled the miRNA expression by miRNA microarray and identified miR-130b as a potential target of mutant p53. Ectopic expression of p53 mutants repressed the expression of miR-130b and triggered ZEB1-dependent EMT and cancer cell invasion. Loss of an endogenous p53 mutation increased the expression of miR-130b, which resulted in reduced ZEB1 expression and attenuation of the EMT phenotype. Furthermore, re-expression of miR-130b suppressed mutant p53-induced EMT and ZEB1 expression. Importantly, the expression of miR-130 was significantly reduced in EC tissues, and patients with higher expression levels of miR-130b survived longer. These data provide a novel understanding of the roles of p53 gain-of-function mutations in accelerating tumor progression and metastasis through modulation of the miR-130b-ZEB1 axis.
Large-strain ausforming and low-temperature bainite transformation were carried out in a medium C - Si rich alloy steel on a thermomechanical simulator. Then, temperature–time–transformation curves ...of the bainite transformation after ausforming at different temperatures were obtained by dilatometry. The effects of ausforming on transformation kinetics, microstructure, and hardness of samples were studied. Results show that the entire process of bainite transformation can be accelerated by ausforming. With decreasing ausforming temperature, the transformation rates greatly increased at the initial transformation stage but slightly decreased at the final stage. Compared with non-ausformed sample, not only was the maximum growth rate in the ausformed samples larger, but the maximum growth rate also appeared earlier. In addition, the maximum rate of the ausformed bainite transformation was increased and the time of reaching the maximum rate was shortened with decreasing the ausforming temperature. The effect of ausforming on bainite transformation kinetics depended not only on the ausforming temperature and strain but also on the isothermal transformation temperature. The reduction in transformation time was increased under decreased isothermal transformation temperature. Ausforming refined the bainite plates and increased the fraction of retained austenite formed in the subsequent low-temperature isothermal transformation. Consequently, nanostructured bainite with enhanced hardness was prepared in the medium C - Si rich alloy steel.
The co-deformation and shear localization in heterophase alloys is studied using two-dimensional crystal plasticity finite element simulations on plane strain compressed Cu–Ag and Cu–Nb metal matrix ...composites. The aim is to study the fundamentals of micromechanics, co-deformation and shear banding in materials with heterophase interfaces. It is observed that, depending on the initial orientations of the crystals, co-deformation of the constituent heterophases often proceeds via collective mechanisms, i.e. by pronounced shear banding triggered by stress concentration at the interfaces. This phenomenon leads to highly localized strains within the bands, exceeding the average strain in part by two orders of magnitude. Shear band development is related to the inherent mechanical properties of each crystal and also to the properties of the abutting crystals. The predicted topology and nature of the cross-phase shear bands, i.e. the extreme local strains, significant bending of the interface regions, and sharp strain localization that propagates across the interfaces, agree well with experimental observations in cold-rolled composites. The simulations reveal that cross-phase shear banding leads to large and highly localized values of stress and strain at heterophase interfaces. Such information is essential for a better understanding of the micromechanical boundary conditions inside co-deformed composites and the associated shear-induced chemical mixing.
Heterophase interfaces play a crucial role in deformation microstructures and thus govern mechanical properties of multilayered composites. Here, we fabricated Ti/Nb multilayers by accumulative roll ...bonding (ARB) where shear bands became predominant with increasing rolling cycles. To explore correlation between micromechanical behavior and mechanical properties of the composites with various lamellar morphologies, in-situ high-energy X-ray diffraction tensile tests were performed. The results quantitatively reveal that the rapid strengthening of the composites with increasing ARB cycles mainly originates from the Nb layers strengthened by dislocations, grain boundaries and heterophase interfaces, and the {211} grains mostly contribute to the global strain hardening. The softer Ti grains also extend global strain hardening to a wide range and postpone necking. Furthermore, complete stress state analysis show that in the presence of extensive shear bands, significant load partitioning between the neighboring metals leads to triaxial stresses in each constituent and dislocations tend to slip along the shear direction. This promotes dislocation multiplication and motion, which is conducive to overall strength enhancement while maintaining a satisfactory ductility. These findings elucidate the effect of strong constraints of the interfaces on mechanical properties, which provides a fundamental understanding of load partitioning and strengthening mechanisms of the multilayers processed by multiple ARB cycles.
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We studied the texture and microstructure evolution in a plane strain compressed Cu–Ag metal matrix composite (MMC) with a heterophase microstructure using crystal plasticity finite element ...simulations. Lattice reorientations induced by both crystallographic (dislocation slip and twinning) and non-crystallographic (shear banding) mechanisms are addressed. First, simulations on a polycrystalline composite are made. Quite similar texture trends are observed for the composites and for the individual single-phase materials, namely, copper-type texture components in the Cu phase and brass-type texture components in the Ag phase. This result differs from experimental data that show less copper-type and more brass-type textures in both phases for the composite materials. To explore co-deformation mechanisms that lead to the specific crystallographic textures in the MMC, bicrystal simulations for the composite with specific initial orientation combinations are performed. The bicrystal simulations reproduce the experimentally observed trends of texture evolution in the respective phases of the composite, indicating that the localized stress and strain fields as well as the co-deformation mechanisms within the actual heterophase microstructure are well captured. The modeling shows that to accommodate plastic deformation between adjacent phases in the bicrystals, pronounced shear bands are triggered by stress concentration at the hetero-interfaces. With further deformation the bands penetrate through the phase boundaries and lead to larger lattice rotations. The simulations confirm that the shear banding behavior in heterophase composites is different from that in single-phase metals and the texture evolution in composite materials is strongly influenced by the starting texture, the local constraints exerted from the phase boundaries and the constitutive properties of the abutting phases.
In this study we explored mechanisms for improving the mechanical properties and retained-austenite (RA) stability of a Q&P steel by adjusting the phase ratio. With increasing annealing temperature, ...the yield strength of the steel increased and the ductility firstly increased and then decreased. These observations are closely related to the specific phase constituent and retained austenite stability produced by the Q&P process. The hard phase (tempered martensite, bainite, martensite-austenite island/secondary martensite) fraction increased with increasing annealing temperature, and the RA size and morphology changed from large, blocky to small, blocky and lath-like. At 800 °C, the phase ratio of RA, bainite, ferrite, and initial martensite is 2:1:2.2:2, which produced the superior combinations of yield strength (σy), tensile strength (σTS), and ductility (δ) (e.g. σy = 960 MPa, σTS = 1450 MPa, δ = 28%; or σy = 1320 MPa, σTS = 1540 MPa, δ = 14%). The superior mechanical properties are attributed to the coordinated deformation between hard phase and soft phase and TRIP effect.
In the United States, high rates of HIV infection among persons who engage in transactional sex are partially driven by substance use. Little is known about transactional sex among rural populations ...of people who inject drugs (PWID). Using data from a 2018 survey of 420 rural PWID in West Virginia, we used logistic regression to identify correlates of recent transactional sex (past 6 months). Most study participants were male (61.2%), white (83.6%), and reported having injected heroin (81.0%) in the past 6 months. Nearly one-fifth (18.3%) reported engaging in recent transactional sex. Independent correlates of transactional sex were: being female adjusted odds ratio (aOR) 3.90; 95% CI 2.12–7.16; being a sexual minority (aOR 3.07; 95% CI 1.60–5.87); being single (aOR 3.22; 95% CI 1.73–6.01); receptive syringe sharing (aOR 3.13; 95% CI 1.73–5.66); and number of injections per day (aOR 1.08; 95% CI 1.01–1.15). Rural PWID who engage in transactional sex are characterized by multiple vulnerabilities that increase their HIV risk.
The study of toughening mechanism associated with the heat-affected zone (HAZ) continues to be of significant interest for improving the low temperature (−40 °C) toughness. In this study, the effect ...of different heat input on microstructure, hardness and low temperature impact toughness of coarse-grained HAZ (CGHAZ) in a high-strength low-alloy (HSLA) plate steel was explored by using welding thermal simulations. After different welding thermal cycles with heat input of 60, 90, 120, and 180 kJ cm−1, average effective grain size of 5.7, 5.9, 6.2, and 6.7 ± 0.2 μm, were respectively obtained. Although the effective grain size marginally increased with the increase of heat input, the values were remarkably smaller than the prior austenite grain size of 54, 93, 104, and 118 μm. Compared to the as-processed HSLA steel, impact toughness of steel welded with a heat input of 60 kJ cm−1 decreased dramatically from 318 ± 20 to 31 ± 8J·cm−2. But interestingly, impact toughness was increased to a peak value of 325 ± 20 J cm−2 when the heat input was increased to 180 kJ cm−1. Toughness was enhanced by grain refinement (D = 6.7 ± 0.2 μm) and through the nano-size precipitates (d = 10 nm), which were induced by medium heat input of 180 kJ cm−1. The values of precipitation strengthening were 203 MPa and 90 MPa while the critical stress values of crack propagation were 32 GPa and 10 GPa for the steels welded at 180 and 270 kJ cm−1, respectively. A critical analysis of fracture toughness and yield strength in terms of theoretical predictions is presented.
In this study, the microstructure and mechanical properties of the 0.56 wt % C transformation-induced plasticity (TRIP) steel are investigated by conducting tensile tests at a wide span of ...deformation temperatures (25–400 °C) and strain rates (0.001–1 s−1). The target is to explore the stability of retained austenite (RA) at various temperatures and strain rates, and the influence of the RA stability on the TRIP effect. Tensile strength decreases with the increasing deformation temperature at a constant strain rate. When temperature changes from 200 °C to 300 °C, tensile strength increases from 1154 ± 10 MPa to 1227 ± 10 MPa. Interestingly, at 300 °C the total elongation at a strain rate of 0.01s−1 can reach 90%, which is twice than that at 25 °C. Moreover, the deformation induced precipitation of carbides reduces the stability of RA, promoting the martensitic transformation. This process counteracts the suppressed TRIP effect with the increase of temperatures. The newly formed precipitates effectively increase work hardening. Thus the TRIP effect and precipitation strengthening jointly lead to excellent mechanical properties of the steel at 300 °C. After deformation, the volume fraction of RA increases with the increasing strain rate at constant temperatures, suggesting that the increasing strain rate suppresses the transformation from RA to martensite.
•Only 40 % of AI/ANs in specialty OUD care receive medication treatments.•Only 22 % of specialty treatment facilities serving AI/ANs offer opioid agonists.•AI/ANs access medications in specialty care ...at similar rates as other race groups.•AI/ANs in opioid treatment have higher rates of methamphetamine co-use.•AI/ANs in the South or justice-referred are least likely to receive medications.
American Indians and Alaska Natives (AI/ANs) are disproportionately affected by the opioid overdose crisis. Treatment with medications for opioid use disorder (MOUD) can significantly reduce overdose risk, but no national studies to date have reported on the extent to which AI/ANs access these treatments overall and in relation to other groups.
The current study used two national databases - the 2018 National Survey on Substance Abuse Treatment Services and the 2017 Treatment Episode Dataset - to estimate the extent to which MOUD is available and used among AI/ANs across the U.S.
We found that facilities serving AI/ANs (N = 1,532) offered some MOUD at similar rates as other facilities (N = 13,277) (39.6 vs. 40.6 %, p = 0.435) but were less likely to offer the standard of care with buprenorphine or methadone maintenance (22.4 % vs. 27.6 %, p < 0.001). AI/AN clients in specialty treatment (N = 8,136) exhibited slightly higher MOUD use (40.0 % vs. 38.6 %, p = 0.009) relative to other race groups (N = 673,938). AI/AN clients were also more likely to exhibit greater prescription opioid use and methamphetamine co-use relative to other groups. AI/AN clients in the South (aOR:0.2395 %CI: 0.19−0.28 or referred by criminal justice sources (aOR:0.1395 %CI: 0.11−0.16 were least likely to receive MOUD.
We conclude that most AI/ANs in specialty treatment do not receive medications for opioid use disorder, and that rates of MOUD use are similar to those of other race groups. Efforts to expand MOUD among AI/ANs that are localized and cater to unique characteristics of this population are gravely needed.