Physically based constitutive equations incorporating the key microstructural mechanisms e.g. dislocations, grain size, etc, have been used widely to predict the stress-strain behaviour of alloys at ...plastic and viscoplastic conditions. This enables an accurate prediction of the formed geometry as well as the final underlying microstructures. However, these physically based constitutive equations have not been practically validated due to the lack of systematic experimental data at microscopic scale. This leads to a large number of unknown constants required to be determined through various optimization algorithms. The aim of this paper is to provide direct and systematic experimental data by revealing the dislocation (geometrically necessary one) density and grain size evolution of AA6082, which is a widely used high-strength aluminium alloy for automobile structural panels, as functions of strain, strain rate and temperature, and is the first-time using Electron Back Scattering Diffraction (EBSD) technique to visualize the microstructures during the hot deformation. The evolution of the dislocation accumulation during the hot tensile deformation at 300, 450, 530 °C using various strain rates (i.e. 1/s, 0.1/s, 0.01/s) was achieved. EBSD maps were analysed on samples submitted to a true strain level of ~0.1 and ~0.3 under each condition. These maps cover >3000 grains and enable to capture the statistical nature of the geometrically necessary dislocation densities during hot deformation. Despite the rapidly plateaued flow stress curves at high temperatures, a continuously increased average GND density was observed in AA6082 with the imposed true strain levels under all conditions. Dislocation channel structures were observed in the hot deformed samples. Dynamic recrystallization was also observed, which coupled with the GNDs and affected the hardening behaviour of the flow stress-strain curves. This work is the first study, using EBSD, to visualize the high temperature and high strain rate induced dislocation distributions over a relatively large area, providing valuable data that may be used for subsequently improving and calibrating the physically based material models.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 ...viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and β-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin–angiotensin–aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill’s causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.
Twinning and shear bands are two main deformation structures in magnesium alloys at low temperatures, however, the relationship between these two deformation structures is still under debate. To ...clarify their relationship and behaviours at low temperatures, rolling tests to various thickness reductions at room temperature (RT) and liquid nitrogen temperature (LNT) were conducted for AZ31 magnesium alloys. The evolutions of shear bands and twinning, and their interactions with geometrically necessary dislocation (GND), were observed during the RT- and LNT-rolling process. Abundant shear bands, evolving from {101¯1}-{101¯2} double twins (DTWs), were observed in the RT-rolled samples, while a high quantity of twins, including {101¯2} tension twins (TTWs), twin-twin interactions and twinning sequence, were observed in the LNT-rolled samples. More importantly, a rarely observed twinning sequence behaviour, namely primary TTW-TTW interactions→ secondary TTW-TTW interactions, creating a 45° <202¯1¯> misorientation peak, was studied. Abundant GNDs accumulated around these twin-twin interactions, twinning sequence, DTWs and shear bands, while the GND density was low around TTWs. This research delivers a systematic investigation into the deformation structures in Mg alloys during the rolling process from RT to cryogenic temperature and provides insights into the newly discovered twinning sequence and twin-twin interactions.
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•A new twinning sequence, namely primary twin-twin interactions → secondary twin-twin interactions, was discovered.•The rolling at cryogenic temperature was accommodated by tension twins → twin-twin interactions → twinning sequence.•Regarding rolling at room temperature, the deformation was governed by double twins → shear bands.•The geometrically necessary dislocation density was high in twin-twin interactions, twinning sequence and shear bands.
Nanotechnology has allowed the construction of various nanostructures for applications, including biomedicine. However, a simple target-specific, economical, and biocompatible drug delivery platform ...with high maximum tolerated doses is still in demand. Here, we report aptamer-tethered DNA nanotrains (aptNTrs) as carriers for targeted drug transport in cancer therapy. Long aptNTrs were self-assembled from only two short DNA upon initiation by modified aptamers, which worked like locomotives guiding nanotrains toward target cancer cells. Meanwhile, tandem “boxcars” served as carriers with high payload capacity of drugs that were transported to target cells and induced selective cytotoxicity. aptNTrs enhanced maximum tolerated dose in nontarget cells. Potent antitumor efficacy and reduced side effects of drugs delivered by biocompatible aptNTrs were demonstrated in a mouse xenograft tumor model. Moreover, fluorophores on nanotrains and drug fluorescence dequenching upon release allowed intracellular signaling of nanotrains and drugs. These results make aptNTrs a promising targeted drug transport platform for cancer theranostics.
MicroRNAs are known to be important in a variety of cancer types. The specific expression and roles of miR-338-3p in the context of gastric cancer, however, remains largely unknown. In this study, we ...found that miR-338-3p was expressed significantly lower in established/primary human gastric cancer cells than that in human gastric epithelial cells; miR-338-3p is also decreased in human gastric cancer tissues and was positively associated with the worse prognosis of patients with gastric cancer. Enforced expression of miR-338-3p could inhibit cell growth, survival, and proliferation, while inducing cell apoptosis. In addition, miR-338-3p negatively regulated SOX5 expression through directly binding to the 3′-untranslated region of SOX5, and an inverse correlation was found between miR-338-3p and SOX5 messenger RNA expression in gastric cancer tissues. Furthermore, miR-338-3p-induced inactivation of Wnt/β-catenin signaling was greatly abrogated by SOX5 upregulation. Finally, we found that hypoxic conditions were linked with reduced miR-338-3p expression in the context of gastric cancer. In conclusion, miR-338-3p acts as a tumor suppressor in gastric cancer, possibly by directly targeting SOX5 and blocking Wnt/β-catenin signaling. These findings might provide novel therapeutic targets for gastric cancer.
The mechanical behaviours of magnesium alloy (WE43) at cryogenic temperatures are investigated. The significant improvement in both fracture strength (28%) and strain-to-failure (24%) at −196 °C is ...observed when compression direction is normal to the extrusion direction, as benchmarked against room-temperature properties. This considerable improvement in strain-to-failure and strength at cryogenic temperature is attributed to unusual enhanced pyramidal slip.
Despite the role of polyploidy in multiple evolutionary processes, its impact on plant diversification remains controversial. An increased polyploid frequency may facilitate speciation through shifts ...in ecology, morphology or both. Here we used Allium to evaluate: (1) the relationship between intraspecific polyploid frequency and species diversification rate; and (2) whether this process is associated with habitat and/or trait shifts.
Using eight plastid and nuclear ribosomal markers, we built a phylogeny of 448 Allium species, representing 46% of the total. We quantified intraspecific ploidy diversity, heterogeneity in diversification rates and their relationship along the phylogeny using trait-dependent diversification models. Finally, we evaluated the association between polyploidisation and habitat or trait shifts.
We detected high ploidy diversity in Allium and a polyploidy-related diversification rate shift with a probability of 95% in East Asia. Allium lineages with high polyploid frequencies had higher species diversification rates than those of diploids or lineages with lower polyploid frequencies. Shifts in speciation rates were strongly correlated with habitat shifts linked to particular soil conditions; 81.7% of edaphic variation could be explained by polyploidisation.
Our study emphasises the role of intraspecific polyploid frequency combined with ecological drivers on Allium diversification, which may explain plant radiations more generally.
Background Nasal polyps (NPs) are characterized by eosinophilic inflammation, which is generally considered sensitive to corticosteroid treatment. Objectives We evaluated levels of neutrophilia in ...NPs and investigated whether increased neutrophilia in polyp tissue affected the response to corticosteroid treatment. Methods We studied 3 independent cross-sectional groups of patients with NPs. Levels of infiltration by different types of inflammatory cells were determined by using immunohistochemical analyses and compared with those seen in control nasal tissues from subjects without NPs. Levels of inflammatory mediators were measured by using real-time PCR, ELISA, and FlowCytomix analyses. Patients with NPs received oral corticosteroid therapy (30 mg of prednisone once daily for 7 days); clinical parameters of efficacy were associated with NP phenotypes. Results Among patients with NPs, 76.5% had an eosinophilic phenotype, 46.0% had a neutrophilic phenotype, and 35.8% had a mixed phenotype (indicated by double staining). Overall, patients' symptoms improved after corticosteroid treatment; numbers of eosinophils and levels of their mediators (IL-4 and IL-5), but not numbers of neutrophils or levels of their mediators (IL-8 and interferon-inducible protein 10), were reduced ( P < .05). After corticosteroid treatment, patients with the nonneutrophilic phenotype (neutrophil negative) had significantly greater reductions in bilateral polyp size scores, nasal congestion scores, total nasal symptom scores, and nasal resistance than patients with the neutrophilic phenotype (neutrophil positive, P < .05). Conclusions There are different phenotypes of NPs based on the type of immune cell infiltrate and cytokines produced (eosinophilic or neutrophilic). Patients with the neutrophilic phenotype have less response to treatment with corticosteroids based on symptom scores.
The nickel-catalyzed decarbonylation of unstrained diaryl ketones has been developed. The reaction is catalyzed by a combination of Ni(cod)2 and an electron-rich N-heterocyclic carbene ligand. High ...functional group tolerance and excellent yields (up to 98%) are observed. This strategy provides an alternative and versatile approach to construct biaryls using an inexpensive nickel catalyst.
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