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The grain size achievable and long-term stability of a severely deformed aluminium copper alloy have been investigated when copper is used in solution to inhibit recovery. It is shown that copper is more effective than magnesium in inhibiting dynamic recovery. A grain width of only $70 nm was obtained in an Al-4 wt.% Cu alloy, after processing by equal-channel angular extrusion to a strain of e eff = 10, resulting in a lamellar nanograin structure. However, post-processing, the severely deformed solid solution was found to be unstable at room temperature and copious precipitation of h occurred at grain boundaries within the deformed state, leading to recovery of the deformation structure and a loss of strength. The solute level fell to equilibrium within $9 months. The precipitation kinetics were shown to occur at many orders of magnitude higher than can be predicted by classical nucleation and growth theory. The reasons for this discrepancy are discussed.

Characterization of microstructures containing small grains or low-angle grain boundaries by electron backscattered diffraction (EBSD) is limited by the spatial and angular resolution limits of the technique. It was found that the best effective spatial resolution (60 nm) for aluminium alloys in a tungsten-filament scanning electron microscope (SEM) was obtained for an intermediate probe current which provided a compromise between pattern quality and specimen interaction volume. The same specimens and EBSD equipment when used with a field-emission gun SEM showed an improvement in spatial resolution by a factor of 2-3. For characterizing low-angle boundary microstructures, the precision of determining relative orientations is a limiting factor. It was found that the orientation noise was directly related to the probe current and this was interpreted in terms of the effect of probe current on the quality of the diffraction patterns.

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With the aim of investigating the factors that limit the production of true nanograined materials by cryogenic severe deformation, the grain structures formed in an Al-0.1%Mg alloy have been studied in plane strain compression at temperatures down to 77 K, following prior severe plastic deformation (SPD) by equal channel angular extrusion. Changing the deformation mode alone had little effect on increasing the rate of grain refinement. At the minimum cryogenic temperature (77 K) the samples still contained $30% low angle boundaries and a nanoscale high-angle boundary (HAB) spacing was only obtained in one dimension. At high strains a steady-state minimum HAB spacing was approached, irrespective of the temperature, where the rate of grain refinement stagnated. It is shown that the minimum grain size achievable in SPD is limited by a balance between the rate of compression of the HAB spacing and dynamic grain coarsening. At low temperatures this is controlled by abnormally high boundary migration rates, which are difficult to explain with existing theories of grain boundary mobility.

BackgroundAccording to recent clinical observations, deficient DNA mismatch repair (dMMR) is capable of improving antitumor effects of the PD-1/PD-L1 pathway, suggesting that dMMR may act as a prognostic indicator of PD-1/PD-L1 antibody drugs. In this study, we examined the dMMR and PD-1/PD-L1 expression, as well as explored the correlation of dMMR status with PD-1/PD-L1 expression in cervical cancer patients, in order to optimize cervical cancer patient selection for PD-1/PD-L1 antibody drug treatment, which is helpful to avoid adverse effects and keep costs manageable.MethodsSixty-six tissue samples from patients with squamous cell carcinoma were collected, and data of their clinical characteristics were also gathered. Based on these samples, the expression levels of MLH1, MSH2, and PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Moreover, PD-1/PD-L1 expression in tumor-invading lymphocytes (TILs) was detected by IHC as well. Six single-nucleotide-repeat markers of microsatellite instability (MSI), including NR-27, MONO-27, BAT-25, NR-24, NR-21, and BAT-26, were tested by capillary electrophoresis sequencer analysis. According to expression of MLH1, MSH2 and the MSI test, all 66 cases were divided into dMMR or proficient DNA mismatch repair (pMMR) groups. The comparisons of dMMR and PD-L1 in cancer cells and of PD-1/PD-L1 in TILs were conducted categorized by age, childbearing history, history of abortion, ethnicity, and cancer cell differentiation subgroup. Furthermore, PD-L1 levels in cancer cells and PD-1/PD-L1 in TILs were analyzed and compared in both dMMR and pMMR subgroups.ResultsOf the patient samples, 25.8% were associated with dMMR. PD-L1 in cancer cells, PD-L1 in TILs, and PD-1 in TILs took up 59.1%, 47.0%, and 60.6%, respectively. The data indicated that both dMMR and PD-L1 overexpression resulted from lower cancer differentiation, more incidences of childbearing, and a history of abortion. Abortion could significantly increase PD-1 expression levels in TILs. Additionally, more incidence of childbearing or older age (35–55 years) was able to upregulate PD-L1 expression in TILs. Statistical difference of PD-L1 in cancer cells could be observed between dMMR and pMMR subgroups. In the dMMR group, PD-L1 in cancer cells and PD-1 in TILs had no correlation (rs=0.161, p=0.537), but in the pMMR group, they had good correlation (rs=0.645, p<0.001).ConclusionAccording to prior studies and our own experiments, PD-L1 in both cancer cells and TILs and PD-1 in TILs are widely observed in cervical cancer patients, indicating that there may be potential to apply PD-1/PD-L1 antibody drugs in cervical cancer. dMMR patients are associated with higher PD-L1 expression compared with pMMR ones, which suggested that PD-1/PD-L1 antibody drugs may work well in dMMR cervical cancer patients. Moreover, in patients with more incidences of childbearing or abortion, dMMR may be a molecular detection target for clinical application of PD-1/PD-L1 antibody drugs.

This review presents the operation procedures of commonly used standard methods for assessment of Mg-based biomaterials from bench to clinic.