Surprising increase in yield stress of Mg single crystal using long-period stacking ordered nanoplates

Mg–Zn–Y ternary alloys containing the long-period stacking ordered (LPSO) phase exhibit superior mechanical properties. This is believed to be originating from the LPSO phase acting as the strengthening phase. However, we first clarify that the mechanical properties of the matrix Mg solid solution in the Mg/LPSO two-phase alloy are significantly different from those of pure Mg. The yield stress of a Mg99.2Zn0.2Y0.6 single crystal (matrix Mg solid solution) is almost the same as that of an LPSO single-phase alloy. This is ascribed to the formation of thin stacking-fault-like defects, named “LPSO nanoplate”. In Mg99.2Zn0.2Y0.6, kink-band formation is induced in the same manner as that in the LPSO phase in deformation, resulting in high strength accompanied with increased ductility. Our results suggest that the strengthening mechanism of the Mg/LPSO two-phase alloy must be reconsidered depending on the microstructure. Furthermore, the results suggest that new ultrahigh-strength Mg alloys, which have much lower Zn and Y contents but the mechanical properties are comparable or superior than the present Mg/LPSO two-phase alloys, are expected to be developed via the appropriate control of LPSO nanoplate microstructures.Hagihara K., Ueyama R., Yamasaki M., et al. Surprising increase in yield stress of Mg single crystal using long-period stacking ordered nanoplates. Acta Materialia, 209, 116797. https://doi.org/10.1016/j.actamat.2021.116797

Diabetes-Related Ankyrin Repeat Protein (DARP/Ankrd23) Modifies Glucose Homeostasis by Modulating AMPK Activity in Skeletal Muscle.

Skeletal muscle is the major site for glucose disposal, the impairment of which closely associates with the glucose intolerance in diabetic patients. Diabetes-related ankyrin repeat protein (DARP/Ankrd23) is a member of muscle ankyrin repeat proteins, whose expression is enhanced in the skeletal muscle under diabetic conditions; however, its role in energy metabolism remains poorly understood. Here we report a novel role of DARP in the regulation of glucose homeostasis through modulating AMP-activated protein kinase (AMPK) activity. DARP is highly preferentially expressed in skeletal muscle, and its expression was substantially upregulated during myotube differentiation of C2C12 myoblasts. Interestingly, DARP-/- mice demonstrated better glucose tolerance despite similar body weight, while their insulin sensitivity did not differ from that in wildtype mice. We found that phosphorylation of AMPK, which mediates insulin-independent glucose uptake, in skeletal muscle was significantly enhanced in DARP-/- mice compared to that in wildtype mice. Gene silencing of DARP in C2C12 myotubes enhanced AMPK phosphorylation, whereas overexpression of DARP in C2C12 myoblasts reduced it. Moreover, DARP-silencing increased glucose uptake and oxidation in myotubes, which was abrogated by the treatment with AICAR, an AMPK activator. Of note, improved glucose tolerance in DARP-/- mice was abolished when mice were treated with AICAR. Mechanistically, gene silencing of DARP enhanced protein expression of LKB1 that is a major upstream kinase for AMPK in myotubes in vitro and the skeletal muscle in vivo. Together with the altered expression under diabetic conditions, our data strongly suggest that DARP plays an important role in the regulation of glucose homeostasis under physiological and pathological conditions, and thus DARP is a new therapeutic target for the treatment of diabetes mellitus

Loading orientation dependence of the formation behavior of deformation kink bands in the Mg-based long-period stacking ordered (LPSO) phase

The variation in the deformation behavior of a directionally solidified (DS) Mg-based long-period stacking ordered (LPSO)-phase crystal depending on the loading orientation was examined. The frequency of formation of the beak-like shape of the deformation band, which is known as one of the important deformation mechanisms in the LPSO phase, monotonically decreased as the inclination angle of the loading orientation with respect to the crystal growth direction in the DS crystal increased, and was accompanied by a decrease in the yield stress due to the activation of basal slip. Deformation bands formed along a direction approximately perpendicular to the grain boundary independent of the loading orientation. The crystal rotation axes selected in the deformation bands were perpendicular to [0001] in almost all grains, independent of the loading orientation. However, the rotation axes in the bands were not fixed but varied between h1010 - i and h1120 - i; this variation was correlated with the loading axis. These observed features strongly suggest that the deformation bands formed in the LPSO phase are predominantly deformation kink bands and that the formation mechanism itself does not vary with the loading orientation but instead its details. The selectivity of the crystal rotation axis in the kink band is strongly affected by the loading orientation.Hagihara K., Okamoto T., Ueyama R., et al. Loading orientation dependence of the formation behavior of deformation kink bands in the Mg-based long-period stacking ordered (LPSO) phase. Materials Transactions 61, 1821 (2020); https://doi.org/10.2320/matertrans.MT-MM2019001

Quantitative estimation of kink-band strengthening in an Mg–Zn–Y single crystal with LPSO nanoplates

Kink-band strengthening was first quantitatively evaluated using an Mg–Zn–Y single crystal containing long-period stacking ordered (LPSO) nanoplates. The ability of a kink-band boundary to act as a barrier that hinders the motion of dislocations is high and comparable to that of a general random grain boundary. Nevertheless, a kink-band boundary is regarded as a simple tilt boundary in the dislocation model. One reason for the anomalous ability of kink-band boundary acting as barriers is related to its peculiar hierarchical structure, in which many small kink bands with high crystal rotation angles accumulate in a localized region.Hagihara K., Ueyama R., Tokunaga T., et al. Quantitative estimation of kink-band strengthening in an Mg–Zn–Y single crystal with LPSO nanoplates. Materials Research Letters, 9, 11, 467. https://doi.org/10.1080/21663831.2021.1974593

Autosynchronized systolic unloading during left ventricular assist with a centrifugal pump

AbstractObjectives: The purpose of this study was to investigate how the inflow cannulation site of the left ventricular assist system with a centrifugal pump would influence cardiac function on failing heart models. Methods: In 10 sheep, a left ventricular assist system was instituted by an outflow cannula in the descending aorta, two inflow cannulas in the left atrium and the left ventricle, and connecting those cannulas to a magnetically suspended centrifugal pump. A conductance catheter and a tipped micromanometer for monitoring the pressure-volume loop were also inserted into the left ventricle. Myocardial oxygen consumption was directly measured. Heart failure was induced by injection of microspheres into the left main coronary artery. The assist rate was varied from 0% to 100% at each inflow cannulation site. Results: The pump flow with left ventricular cannulation increased during the systolic phase and decreased during the diastolic phase, whereas it was constant with left atrial cannulation. Ejection fraction with left atrial cannulation decreased as the assist rate increased, whereas that with left ventricular cannulation was maintained up to 75% assist. The external work with left atrial cannulation decreased gradually as the assist rate increased, whereas the external work with left ventricular cannulation did not decrease until the assist rate reached 75%. The myocardial oxygen consumption in both cannulations decreased proportionally as the assist rate increased; they were significantly less with left ventricular cannulation at the 100% assist rate than with left atrial cannulation. Conclusion: Left ventricular cannulation during left ventricular assistance maintains ejection fraction and effectively reduces oxygen consumption.J Thorac Cardiovasc Surg 2003;125:353-6

PARM-1 Is an Endoplasmic Reticulum Molecule Involved in Endoplasmic Reticulum Stress-Induced Apoptosis in Rat Cardiac Myocytes

To identify novel transmembrane and secretory molecules expressed in cardiac myocytes, signal sequence trap screening was performed in rat neonatal cardiac myocytes. One of the molecules identified was a transmembrane protein, prostatic androgen repressed message-1 (PARM-1). While PARM-1 has been identified as a gene induced in prostate in response to castration, its function is largely unknown. Our expression analysis revealed that PARM-1 was specifically expressed in hearts and skeletal muscles, and in the heart, cardiac myocytes, but not non-myocytes expressed PARM-1. Immunofluorescent staining showed that PARM-1 was predominantly localized in endoplasmic reticulum (ER). In Dahl salt-sensitive rats, high-salt diet resulted in hypertension, cardiac hypertrophy and subsequent heart failure, and significantly stimulated PARM-1 expression in the hearts, with a concomitant increase in ER stress markers such as GRP78 and CHOP. In cultured cardiac myocytes, PARM-1 expression was stimulated by proinflammatory cytokines, but not by hypertrophic stimuli. A marked increase in PARM-1 expression was observed in response to ER stress inducers such as thapsigargin and tunicamycin, which also induced apoptotic cell death. Silencing PARM-1 expression by siRNAs enhanced apoptotic response in cardiac myocytes to ER stresses. PARM-1 silencing also repressed expression of PERK and ATF6, and augmented expression of CHOP without affecting IRE-1 expression and JNK and Caspase-12 activation. Thus, PARM-1 expression is induced by ER stress, which plays a protective role in cardiac myocytes through regulating PERK, ATF6 and CHOP expression. These results suggested that PARM-1 is a novel ER transmembrane molecule involved in cardiac remodeling in hypertensive heart disease

Urinary excretion of 3-phenoxybenzoic acid in middle-aged and elderly general population of Japan

Nagoya University, Department of Medical Technology金沢大学附属病院薬剤部Limited data are available on the background levels of exposure to synthetic pyrethroid (PYR) in Japan, despite their frequent application for agriculture and indoor extermination and possible effects of chronic and/or low-dose PYR exposure on human health. This study was conducted to describe the level and distribution of one of the major PYR metabolites, 3-phenoxybenzoic acid (3-PBA), in urine samples collected from a general population in Japan. The subjects were 535 individuals (184 men and 351 women; 61.5±9.8 years of age, mean±S.D.) residing in a town in Hokkaido, a dairy and agricultural area. Urinary 3-PBA was found detectable in 98% of samples above the limit of detection of 0.02 μg/l. The geometric mean values of urinary 3-PBA in occupationally exposed farmers (n=87) and the remaining general group without occupational exposure (n=448) were 0.38 and 0.29 μg/l, respectively, ranging from <LOD to 17.09 μg/l. No significant differences in urinary 3-PBA concentrations were shown between these two groups. Moreover, 3-PBA concentrations were found comparable to those reported in some countries. The present study is, to our knowledge, the first report of a biological monitoring study of urinary 3-PBA, which elucidated the background environmental exposure level of PYR in the Japanese general population without occupational exposure. Further nationwide studies covering different seasons and age distribution are needed to monitor the urinary 3-PBA levels in Japan