Synthesis of a Novel D-Glucose-Conjugated 15-Crown-5 Ether with a Spiro Ketal Structure

Abstract: This paper describes a synthetic approach to a novel D-glucose-conjugated 15-crown-5 ether having a spiroketal structure starting from a 1-C-vinylated glucose derivative. The approach consists of the glycosylation of the vinylated glucose derivative to give an ethyleneoxy spacer derivative using bismuth(III) triflate, the conversion of the 1-C-vinyl group of the glucoside produced into a carboxylic acid group, and the intramolecular condensation between the carboxyl group and the terminal hydroxyl group in the ethyleneoxy spacer. A D-glucose-conjugated 15-crown-5 ether having a unique spiroketal structure was thus successfully synthesized

Anomalous Transport Properties in BiS2-based Superconductors LnO1−xFxBiS2 (Ln = Nd, La-Sm)

We report the electronic properties of the layered bismuth-based sulfide superconductors NdO1−xFxBiS2 (x = 0.25, 0.4, and 0.5) and La1−ySmyO0.5F0.5BiS2 (y = 0.1–0.7), which have been studied by investigation of their transport properties and X-ray diffraction. In the lightly carrier-doped NdO1−xFxBiS2 (x = 0.25 and 0.4) and La1−ySmyO0.5F0.5BiS2 (y = 0.3 and 0.4), the resistivity and Hall coefficient exhibit anomalous temperature dependences below TCDW ∼ 130 and 200 K, respectively, suggesting the formation of an energy gap on the Fermi surface associated with charge-density wave (CDW). In NdO1−xFxBiS2 (x = 0.25), the bond angles and bond lengths of the Bi–S pentahedron change their temperature dependences below ∼200 K, suggesting that a lattice instability related to the Bi–S pentahedron exists below ∼200 K, which is much higher than TCDW. These results indicate that the lattice instability of the Bi–S pentahedron can trigger a CDW transition in the low-carrier region of BiS2 superconductors

Pain following COVID-19 vaccination

Pain at the injection site is the most frequent reaction among COVID-19 vaccine recipients, but its characteristics were not fully described yet. The purpose of this study was to investigate multiple domains of pain following BNT162b2 mRNA vaccination. We included 107 subjects undergoing primary shot of the vaccination twice into deltoid muscle with a 3-week interval. They completed 6 sessions of pain assessments, one before the first and second dose (1-0, 2-0), and 1st / 7th day after the first and second dose (1-1 / 1-7, 2-1 / 2-7). Pain visual analog scale (VAS), pain distribution, and pressure pain threshold (PPT) on deltoid muscle were evaluated in each session. The mean VAS (at rest / shoulder motion) was 6.0 / 27.6 mm at 1-1, and 12.8 / 34.0 mm at 2-1. Approximately, 90% of recipients showed localized pain within the upper arm. Percentage change of PPTs at 1-1 and 2-1 was bilaterally (ipsilateral / contralateral) decreased to 87.4 / 89.4% and 80.6 / 91.0%, which was recovered to the baseline level at 1-7 and 2-7. Temporary, mild-to-moderate intensity, localized distribution, concomitant with bilateral mechanical hyperalgesia on the deltoid muscle, were typical pain characteristics following this vaccination. These findings provide a rationale that will be informative for future recipients

キサンチンオキシダーゼ阻害薬febuxostatはNrf2を活性化し脂肪細胞分化を抑制する

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine catabolism that acts as a novel regulator of adipogenesis. In pathological states, xanthine oxidoreductase activity increases to produce excess reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical inducer of antioxidants, which is bound and repressed by a kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. The Keap1-Nrf2 axis appears to be a major mechanism for robust inducible antioxidant defenses. Here, we demonstrate that febuxostat, a xanthine oxidase inhibitor, alleviates the increase in adipose tissue mass in obese mouse models with a high-fat diet or ovariectomy. Febuxostat disrupts in vitro adipocytic differentiation in adipogenic media. Adipocytes appeared at day 7 in absence or presence of febuxostat were 160.8 ± 21.2 vs. 52.5 ± 12.7 (p < 0.01) in 3T3–L1 cells, and 126.0 ± 18.7 vs. 55.3 ± 13.4 (p < 0.01) in 10T1/2 cells, respectively. Adipocyte differentiation was further enhanced by the addition of hydrogen peroxide, which was also suppressed by febuxostat. Interestingly, febuxostat, but not allopurinol (another xanthine oxidase inhibitor), rapidly induced the nuclear translocation of Nrf2 and facilitated the degradation of Keap1, similar to the electrophilic Nrf2 activator omaveloxolone. These results suggest that febuxostat alleviates adipogenesis under oxidative conditions, at least in part by suppressing ROS production and Nrf2 activation. Regulation of adipocytic differentiation by febuxostat is expected to inhibit obesity due to menopause or overeating

First Case of Cytokine Release Syndrome after Nivolumab for Gastric Cancer

Introduction: Cytokine release syndrome (CRS) is a potentially life-threatening systemic disease that has been observed after treatment with antibodies and adoptive T cell therapies. In this case, we observed nivolumab-induced CRS in a patient with gastric cancer. Case Presentation: A 43-year-old male with advanced gastric cancer was treated with nivolumab as a third-line chemotherapy. He had no history of allergies. Eight days after the first administration of nivolumab, fever, tachycardia, appetite loss and increases in liver and biliary enzymes were observed. Computed tomography revealed neither bile duct obstruction nor progression of liver metastases but showed that there was edema of the Gleason sheath. Histopathological analysis of the liver revealed cholestatic liver injury with CD8+ T lymphocyte and macrophage infiltration. Neither viral infection nor autoimmune disease was revealed. His symptoms were similar to those of CRS observed after T cell therapy. We diagnosed his disease as nivolumab-induced liver injury and cholangitis accompanied by CRS based on his serum cytokine levels. Discussion/Conclusion: To the best of our knowledge, this is the first report of nivolumab-induced CRS in a patient with gastric cancer