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The complete mitochondrial genome of theSquatina nebulosawas determined first in the present study. The mitochondrial genome is 16,698 nucleotides, encoding a standard set of 13 protein-coding genes and 2 ribosomal RNA genes, 22 tRNA genes, 1 control region and 1 origin of the light strand replication. The overall base composition ofSquatina nebulosais T 31.4%, C 24.1%, A 30.7%, and G 13.8%, and the A + T content is higher than G + C content. These mitogenome sequence data will play an important role in population genetics and phylogenetic analysis of the Suqatinids. [ABSTRACT FROM PUBLISHER]

There is an unmet clinical need for effective anticoagulant therapies for the management of thromboembolic diseases that are not associated with a relevant risk of bleeding. Asundexian (BAY 2433334) is an oral, direct, small-molecule inhibitor of activated factor XI (FXIa). Phase I data from healthy Caucasian male participants indicated predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles and no clinically relevant bleeding-related adverse events (AEs). Reported here are data from two phase I, randomized, placebo-controlled, single- and multiple-dose escalation studies of asundexian conducted in 60 healthy men: 24 Japanese and 36 Chinese. Baseline characteristics were comparable between the treatment groups. All treatment-emergent AEs were mild, with no serious AEs or AEs of special interest reported. Systemic exposure to asundexian increased dose proportionally after single or multiple dosing, with relatively low accumulation following multiple once-daily dosing in both Chinese and Japanese volunteers. Asundexian induced dose-dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants., (© 2024 Bayer AG. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Primary biliary cholangitis (PBC) is characterized as interlobular bile duct injury and fibrosis, which results from the loss of tolerance to self-antigens. However, the exact pathologic mechanism leading to injury and fibrosis in PBC patients is not fully understood. Therefore, in this study, we examined the role of the T cell subsets in PBC patients and healthy controls (HCs). A higher number of invariant Natual killer T (iNKT) cells as well as CD3 + CD56 + αGalcer-CD1d tetramer - T cells were found in patients with PBC compared with HCs. Moreover, these 2 T subpopulations produced significantly higher levels of Interleukin (IL)-17A in PBC patients than those in in HCs, which has also been positively correlated with the disease severity. Furthermore, the level of IL-17A produced by these 2 subpopulations was increased after stimulation of the autoantibodies in patients with PBC. Also, the elevated IL-17A levels promoted the PBC-related fibrosis, thus presenting a change in frequencies and functions of these cell phenotypes in the deterioration of the duct damage-related fibrosis. This study clarified PBC patients' distinct T subpopulations characteristics, providing evidence-based diagnostic and therapies for these patients. The correlation between unclassical T subsets and IL-17A may provide a novel target for the immunotherapy of PBC., (©2022 Society for Leukocyte Biology.)

Three new phenolic compounds, coretinphenol (1), coretincone (2), and coretinphencone (3), were isolated from the buds of Coreopsis tinctoria Nutt., together with nine known compounds, including butein (4), okanin (5), isoliquiritigenin (6), maritimetin (7), taxifolin (8), isookanin (9), marein (10), sachalinoside B (11), and 2-phenylethyl-β-d-glucoside (12). The chemical structures of these compounds were elucidated by extensive spectroscopic analysis and on the basis of their chemical reactivity. This work represents the first recorded example of the isolation of compounds 1–3, 6, 7, 9, 11, and 12 from C. tinctoria. Compounds 5–9 showed strong diphenyl(2,4,6-trinitrophenyl)iminoazanium (DPPH) radical-scavenging activity, with IC50 values of 3.35 ± 0.45, 9.6 ± 2.32, 4.12 ± 0.21, 6.2 ± 0.43, and 7.9 ± 0.53 μM, respectively. Compounds 2 and 8 exhibited angiotensin I-converting enzyme inhibitory activity, with IC50 values of 228 ± 4.47 and 145.67 ± 3.45 μM, respectively. The activities of phenolic compounds isolated from C. tinctoria support the medicinal use of this plant in the prevention of cardiovascular diseases.

Background: Three dimensional conformal radiotherapy is one of the important treatment methods for patients aged 65 and older with inoperable non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy of three dimensional conformal radiotherapy in elderly patients with inoperable NSCLC., Methods: Thirty-one patients aged 65 and older with stage II and III NSCLC were treated by three dimensional conformal radiotherapy. Clinical effects, survival rates and pulmonary toxicity were analyzed., Results: The overall response rate (CR+PR) was 87.1% (27/31). The 1, 2 and 3-year survival rates were 83.9% (26/31), 51.6% (16/31), and 25.8% (8/31) respectively. The relation of treatment efficacy and tumor size was observed. Acute radiation pneumonitis occurred in 3.2% (1/31) of the patients. Radiation pulmonary fibrosis occurred in 19.4% (6/31) of the patients., Conclusions: Three dimensional conformal radiotherapy is a safe and effective treatment for elderly patients with inoperable NSCLC and has a high survival rate.