Search

Although metabolic disturbance is a characteristic of diabetic cardiomyopathy (DbCM), the detailed pathogenesis of DbCM remains unknown. We used a heart transplantation (HTx) cohort to explore the effect of diabetes mellitus on heart failure (HF) progression dependent of myocardium. Microscopic and ultramicroscopic pathology were used to depict the pathological features of human myocardium of DbCM. We performed targeted metabolomics to characterize the metabolic phenotype of human DbCM. Transcriptomics data were analyzed and weighted gene co-expression network analysis was performed to explore the potential upstream regulator for metabolic remodeling of DbCM. In vivo and in vitro experiments were further conducted to demonstrate the therapeutic effects and molecular mechanisms. DbCM promoted the progression of HF and increased death or HF-rehospitalization after HTx. Lipid accumulation and mitochondrial fission were the obvious pathological features of DbCM myocardium. The concentrations of C14:0-CoA and C16:1-CoA were significantly increased in the myocardium, and they were positively correlated with the accelerated HF progression and RCAN1 expression in DbCM patients. Knockdown of RCAN1 improved cardiac dysfunction, lipid accumulation, and mitochondrial fission in db/db mice. In vitro studies showed that RCAN1 knockdown improved mitochondrial dysfunction in DbCM cardiomyocytes via the RCAN1-p-Drp1 Ser616 axis. Diabetes is associated with faster progression of HF and causes poor prognosis after HTx, accompanied by metabolic remodeling in the myocardium. Accumulation of long chain acyl-CoA in the myocardium is the metabolic hallmark of human DbCM and is associated with more rapid disease progression for DbCM patients. Upregulation of RCAN1 in the myocardium is associated with the metabolic signatures of DbCM and RCAN1 is a potential therapeutic target for DbCM. [Display omitted] • Diabetes promotes non-diabetic heart failure after heart transplantation. • The increase in acyl-CoA is the metabolic hallmark of diabetic cardiomyopathy. • Knockdown of RCAN1 improved the cardiac function and structure of db/db mice. • RCAN1-p-Drp1 Ser616 axis contributes to mitochondrial dysfunction in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Purpose The aim was to systematically extrapolate the occurrence, risk factors, prognostic characteristics, management and outcome of bone metastases (BM) and skeletal related events (SREs) of breast cancer survivors in the real world clinical setting. Methods A systematic literature search of PubMed, Web of Science, EMBASE OvidSP and EBSCO Academic Search Complete was conducted. Published prospective and retrospective papers investigating BM and SREs in breast cancer patients in non-trial settings were identified and systematically reviewed. Results Twenty-four studies met the inclusion criteria. Incidences of BM based on new diagnosis, length of BM-free interval (BMFI) and number and sites of BM were detected by 17 of 24 studies. Seven studies included in the review were subjected to analyses of risk factors for BM. Developments of SREs regarding the occurrence ratio of total and specific SREs, SERs-free interval (SREFI) and the first-line therapy for SREs were observed in 16 of 24 studies. Out of 5 studies, we extracted uni- and multivariate analysis of risk factor for SREs and out of 16 studies - predictors for survival in breast cancer patients with BM. Conclusions BM and SREs are common problems in non-trial breast cancer populations. Patient demographics, clinical stage, tumor pathological type, molecular receptors status are significantly risk factors for incidence of BM, SREs and the survival. The unique characteristics of BM and SREs in breast cancer patients should be taken into account in future randomized controlled trials, as to optimize individual treatment options and assure a maximally long good quality of life. [ABSTRACT FROM AUTHOR]

The microstructures and mechanical properties of two new aerospace Al-6.00 Mg-0.40Mn-0.12Zr (wt%) alloy sheets, containing 0.10 wt% Sc (low content) and 0.25 wt% Er(cheap), respectively, were investigated by tensile tests and electron microscopy methods. The results showed that microalloying elements were present in the form of core-shell-structured secondary Al 3 (Sc 1−x Zr x) and Al 3 (Er 1−x Zr x) nanoparticles, whose cores were enriched in Sc and Er, respectively. Stable core-shell structured nanoparticles enabled the annealed sheets to retain a completely non-recrystallized structure and strong β-fiber rolling textures. The ultimate tensile strength (UTS), yield strength (YS) and elongation to failure (El f) of the annealed sheets reached 422 ± 1 MPa, 312 ± 6 MPa, and 20.7 ± 1.5% in the Al-Mg-Mn-Sc-Zr alloy, and 404 ± 5 MPa, 283 ± 7 MPa, and 24.2 ± 0.9% in the Al-Mg-Mn-Er-Zr alloy, respectively, both exhibiting high strength and superior ductility. The mean diameters of the spheroidal Al 3 (Sc 1−x Zr x) and Al 3 (Er 1−x Zr x) particles were 12.1 ± 4.2 nm and 20.2 ± 8.4 nm, respectively, meantime, the number densities of the Al 3 (Sc 1−x Zr x) and Al 3 (Er 1−x Zr x) precipitates were (7.7 ± 3.2) × 1013 m2 and (6.4 ± 1.9) × 1012 m2. The higher number density and the smaller particle sizes of the Al 3 (Sc 1−x Zr x) leaded to the higher strength of the Al-Mg-Mn-Sc-Zr alloy. The main strengthening mechanisms from the secondary Al 3 (Sc 1−x Zr x)/Al 3 (Er 1−x Zr x) nanoparticles were associated with the direct Orowan precipitation strengthening and sub-structure strengthening. Based on the results of this paper, enhanced mechanical properties and a reduced cost can be simultaneously achieved with the new Al-Mg-Mn-Zr alloys with low Sc contents or inexpensive Er addition, offering great potential for the development of new high-strength micro-alloyed Al Mg alloys in industrial applications. Unlabelled Image • Successfully prepare two new Al-Mg-Mn alloys with secondary Al 3 (Sc 1−x Zr x) and Al 3 (Er 1−x Zr x) nanoparticles • Characterize the microstructure evolution of new alloy sheets during their preparations • Clarify the existing forms of the combined additions of low-content Sc and Zr or Er and Zr • Discuss the potential for developing new cost competitive Al-Mg-Mn-Sc-Zr/ Al-Mg-Mn-Er-Zr alloys [ABSTRACT FROM AUTHOR]