Increased Serum KL-6 Levels Induced by Pulmonary Mycobacterium Avium Complex Infection in a Patient with RA-associated Lung Disease

KL-6 is a glycoprotein found predominantly on type II pneumocytes and alveolar macrophages, and often shows increased serum levels in patients with interstitial pneumonia. We report a case of mycobacterium avium complex (MAC) infection whose disease activity was correlated with KL-6 levels in serum. During treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) with prednisolone, chest image findings improved in association with decreased KL-6 levels. Following tapering of prednisolone, chest image findings deteriorated again as levels of KL-6 increased, suggesting recurrence of RA-ILD. Bronchoscopic examination revealed active MAC infection. Treatment of MAC infection not only improved chest image findings but also decreased KL-6 levels in serum, suggesting that KL-6 was increased by active MAC infection by itself, not by recurrence of RA-ILD. To the best of our knowledge, this is the first documentation of KL-6 elevation in serum in association with active MAC infection

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

成人T細胞白血病リンパ腫（ATL）におけるゲノム情報と臨床情報を統合したリスクモデルを確立 --ATLの個別化医療を推進--. 京都大学プレスリリース. 2023-04-10.The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3)

A history of mild shocks experienced by the regolith particles on hydrated asteroid Ryugu

Micrometeorites, a possible major source of Earth’s water, are thought to form from explosive dispersal of hydrated chondritic materials during impact events on their parental asteroids. However, this provenance and formation mechanism have yet to be directly confirmed using asteroid returned samples. Here, we report evidence of mild shock metamorphism in the surface particles of asteroid Ryugu based on electron microscopy. All particles are dominated by phyllosilicates but lack dehydration textures, which are indicative of shock-heating temperatures below ~500 °C. Microfault-like textures associated with extensively shock-deformed framboidal magnetites and a high-pressure polymorph of Fe–Cr–sulfide have been identified. These findings indicate that the average peak pressure was -2 GPa. The vast majority of ejecta formed during impact on Ryugu-like asteroids would be hydrated materials, larger than a millimetre, originating far from the impact point. These characteristics are inconsistent with current micrometeorite production models, and consequently, a new formation mechanism is required

Super-Ionic Conductive Magnet Based on a Cyano-Bridged Mn–Nb Bimetal Assembly

A two-dimensional manganese-octacyanoniobate based magnet, Mn^II₃[Nb^IV(CN)₈]₂(4-aminopyridine)₁₀(4-aminopyridinium)₂·12H₂O, was prepared. This compound shows a spin-flip transition with a critical magnetic field value of ca. 200 Oe, which originates from metamagnetism. In addition, an impedance measurement indicates that this compound is a super-ionic conductor with 4.6 × 10^–4 S cm^–1. The observed super-ionic conductivity is explained by the proton conduction (so-called the Grotthuss mechanism) through the hydrogen-bonding network, i.e., Lewis acidity of the Mn ion accelerates the deprotonation of the ligand water molecules, and then the released proton propagates via ligand water molecules, noncoordinated water molecules, and 4-aminopyridinium cations

Thioredoxin-1 Ameliorates Oxygen-Induced Retinopathy in Newborn Mice through Modulation of Proinflammatory and Angiogenic Factors

Oxygen-induced retinopathy (OIR) is an animal model for retinopathy of prematurity, which is a leading cause of blindness in children. Thioredoxin-1 (TRX) is a small redox protein that has cytoprotective and anti-inflammatory properties in response to oxidative stress. The purpose of this study was to determine the effect of TRX on OIR in newborn mice. From postnatal day 7, C57BL/6 wild type (WT) and TRX transgenic (TRX-Tg) mice were exposed to either 21% or 75% oxygen for 5 days. Avascular and neovascular regions of the retinas were investigated using fluorescence immunostaining. Fluorescein isothiocyanate-dextran and Hoechst staining were used to measure retinal vascular leakage. mRNA expression levels of proinflammatory and angiogenic factors were analyzed using quantitative polymerase chain reaction. Retinal histological changes were detected using immunohistochemistry. In room air, the WT mice developed well-organized retinas. In contrast, exposing WT newborn mice to hyperoxia hampered retinal development, increasing the retinal avascular and neovascular areas. After hyperoxia exposure, TRX-Tg mice had enhanced retinal avascularization compared with WT mice. TRX-Tg mice had lower retinal neovascularization and retinal permeability during recovery from hyperoxia compared with WT mice. In the early stages after hyperoxia exposure, VEGF-A and CXCL-2 expression levels decreased, while IL-6 expression levels increased in WT newborn mice. Conversely, no differences in gene expressions were observed in the TRX-Tg mouse retina. IGF-1 and Angpt1 levels did not decrease during recovery from hyperoxia in TRX-Tg newborn mice. As a result, overexpression of TRX improves OIR in newborn mice by modulating proinflammatory and angiogenic factors