Comparison between Matched Related and Alternative Donors of Allogeneic Hematopoietic Stem Cells Transplanted into Adult Patients with Acquired Aplastic Anemia: Multivariate and Propensity Score-Matched Analysis

We retrospectively compared the outcomes of 225 patients with adult acquired aplastic anemia (AA) who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched related donors (MRDs), and those treated by alloHSCT from alternative donors (ADs). Univariate and multivariate analyses of factors associated with survival were performed. Multivariate analysis showed that age at alloHSCT of ≤31 years, MRD, successful engraftment, absence of acute graft-versus-host disease (aGVHD), and platelet engraftment at ≤21 days, were independent predictors of longer survival. In addition, time to aGVHD and cumulative nonrelapse mortality (NRM) were better in MRD than in AD recipients. Using propensity score matching (PSM), we performed a case-control study comparing 25 patients in each group who underwent alloHSCT from MRDs and ADs. Pretransplantation clinical factors were well balanced in either group. Median survival time was similar, and no statistically significant difference in transplantation outcomes was apparent when MRD and AD recipients were compared. In conclusion, our results suggest that alloHSCT from an AD should be considered earlier in adult patients with AA who do not have an MRD

Pseudoalteromone A, a Ubiquinone Derivative from Marine Pseudoalteromonas spp., Suppresses Melanogenesis

An ubiquinone derivative, pseudoalteromone A (1), has been isolated from two marine-derived Pseudoalteromonas spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 μg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes

Ipsilateral Lymphadenopathy After COVID-19 Vaccination in Patients With Newly Diagnosed Breast Cancer

This study aimed to evaluate the imaging and pathological findings in axillary lymph nodes in patients with breast cancer who received concurrent ipsilateral coronavirus disease 2019 (COVID-19) vaccination. Of the 19 women with breast cancer who received concurrent COVID-19 vaccination shot in the arm ipsilateral to breast cancer, axillary lymphadenopathy was observed in 84.2% (16 of 19) of patients on ultrasound (US) and 71.4% (10 of 14) of patients on magnetic resonance imaging (MRI), and 21.0% (4 of 19) of patients were diagnosed with metastasis. Abnormal US and MRI findings of cortical thickening, effacement of the fatty hilum, round shape, and asymmetry in the number or size relative to the contralateral side were noted in more than half of the non-metastatic and metastatic lymph nodes; however, statistical significance was not noted. Axillary lymphadenopathy is commonly observed in patients with breast cancer who receive concurrent ipsilateral COVID-19 vaccination without specific differential imaging features. Thus, understanding the limitations of axillary imaging and cautious interpretation is necessary to avoid overestimation or underestimation of the axillary disease burden.N

Organometallic Iridium(III) Complex Sensitized Ternary Hybrid Photocatalyst for CO2 to CO Conversion

A series of heteroleptic iridium(III) complexes functionalized with two phosphonic acid (-PO3H2) groups ((IrP)-Ir-dfppy, (IrP)-Ir-ppy, (IrP)-Ir-btp, and (IrP)-Ir-piq) were prepared and anchored onto rhenium(I) catalyst (ReP)-loaded TiO2 particles (TiO2/ReP) to build up a new IrP-sensitized TiO2 photocatalyst system (IrP/TiO2/ReP). The photosensitizing behavior of the IrP series was examined within the IrP/TiO2/ReP platform for the photocatalytic conversion of CO2 into CO. The four IrP-based ternary hybrids showed increased conversion activity and durability than that of the corresponding homo- (IrP+ReP) and heterogeneous (IrP+TiO2/ReP) mixed systems. Among the four IrP/TiO2/ReP photocatalysts, the low-energy-light (>500 nm) activated (IrP)-Ir-piq immobilized ternary system ((IrP)-Ir-piq/TiO2/ReP) exhibited the most durable conversion activity, giving a turnover number of >= 730 for 170 h. A similar kinetic feature observed through time-resolved photoluminescence measurements of both (IrP)-Ir-btp/TiO2 and TiO2-free (IrP)-Ir-btp films suggests that the net electron flow in the ternary hybrid proceeds dominantly through a reductive quenching mechanism, unlike the oxidative quenching route of typical dye/TiO2-based photolysis.11Nsciescopu

Sex specific effect of ATPase inhibitory factor 1 on body weight: studies in high fat diet induced obese mice and genetic association studies in humans

Background: Based on the metabolic effect of exogenous ATPase inhibitory factor 1 (IF1) on glucose metabolism, we tested whether IF1 treatment is effective in ameliorating weight gain and whether its effects are sex specific. Methods: HFD-fed C57BL/6 mice were treated with IF1 (5 mg/kg body weight, injected intraperitoneally). The underlying mechanisms of effect of IF1 on body weight were investigated in vitro and in vivo. Associations between genotypes of IF1 and obesity and relevant phenotype were further tested at the population level. Results: Chronic treatment with IF1 significantly decreased body weight gain by regulating food intake of HFD-fed male mice. IF1 activated the AKT/mTORC pathway and modulated the expression of appetite genes in the hypothalamus of HFD-fed male mice and its effect was confirmed in hypothalamic cell lines as well as hypothalamic primary cells. This required the interaction of IF1 with β-F1-ATPase on the plasma membrane of hypothalamic cells, which led to an increase in extracellular ATP production. In addition, IF1 treatment showed sympathetic nerve activation as measured by serum norepinephrine levels and UCP-1 expression in the subcutaneous fat of HFD-fed male mice. Notably, administration of recombinant IF1 to HFD-fed ovariectomized female mice showed remarkable reductions in food intake as well as body weight, which was not observed in wild-type 5-week female mice. Lastly, sex-specific genotype associations of IF1 with obesity prevalence and metabolic traits were demonstrated at the population level in humans. IF1 genetic variant (rs3767303) was significantly associated with lower prevalence of obesity and lower levels of body mass index, waist circumference, hemoglobin A1c, and glucose response area only in male participants. Conclusion: IF1 is involved in weight regulation by controlling food intake and potentially sympathetic nerve activation in a sex-specific manner. © 2020 Elsevier Inc.1