Individual differences in gut microbiota can affect the pharmacokinetics of drugs. Yokukansan is a traditional Japanese kampo medicine used to treat peripheral symptoms of dementia and delirium. A ...study examining the pharmacokinetics of the components of yokukansan reported large individual differences in the pharmacokinetics of glycyrrhizic acid (GL). It is known that GL is metabolized by intestinal bacteria to glycyrrhetinic acid (GA), which is absorbed in the gastrointestinal tract. Thus, the gut microbiota may affect GL pharmacokinetics. We aimed to clarify the relationship between the gut microbiota composition and pharmacokinetics of GL in yokukansan. Mice were orally administered yokukansan, following the administration of various antibiotics, and the plasma concentration of GA and composition of gut microbiota were measured. The GA plasma concentration was low in mice treated with amoxicillin and vancomycin. The composition of gut microbiota revealed a different pattern from that of the control group. Mice with low plasma levels of GA had lower levels of the phylum Bacteroides and Firmicutes. Additionally, bacteria, such as those belonging to the genera Parabaceroides, Bacteroides, Ruminococcus and an unknown genus in families Lachnospiraceae and Ruminococcaceae, exerted positive correlations between the gene copies and plasma GA levels. These bacteria may contribute to the absorption of GA in the gastrointestinal tract, and multiple bacteria may be involved in GL pharmacokinetics. The pharmacokinetics of GL may be predicted by evaluating the composition of gut bacteria, rather than by evaluating the amount of a single bacterium.
Several studies have established a correlation between the VEGF-VEGFR2 axis and an immunosuppressive microenvironment; this immunosuppression can be overcome by anti-angiogenic reagents, such as ...ramucirumab (RAM). However, little is known about the immunological impact of anti-angiogenic reagents within the tumor microenvironment in human clinical samples. This study aimed at investigating the effects of RAM on the tumor microenvironmental immune status in human cancers.
We prospectively enrolled 20 patients with advanced gastric cancer (GC) who received RAM-containing chemotherapy. We obtained paired samples from peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) in primary tumors both pre- and post-RAM therapy to assess immune profiles by immunohistochemistry and flow cytometry.
Within the tumor microenvironment, both PD-L1 expression and CD8
T-cell infiltration increased after RAM-containing therapies. In addition, CD45RA
FOXP3
CD4
cells (effector regulatory T cells eTreg cells) and PD-1 expression by CD8
T cells were significantly reduced in TILs compared with PBMCs after RAM-containing therapies. Patients with partial response and longer progression-free survival had significantly higher pre-treatment eTreg frequencies in TILs than those with progressive disease. In in vitro analysis, VEGFR2 was highly expressed by eTreg cells. Further, VEGFA promoted VEGFR2
eTreg cell proliferation, and this effect could be inhibited by RAM.
This study suggests that the frequency of eTreg cells in TILs could be a biomarker for stratifying clinical responses to RAM-containing therapies. Further, we propose that RAM may be employed as an immuno-modulator in combination with immune checkpoint blockade.
•Polymer electrolytes consisting of ionomer triblock copolymer and an ionic liquid are prepared.•The tensile properties are greater than those of a nonionic block copolymer electrolyte.•Thermal ...stability, high ionic conductivity, and electrochemical stability is attained.
Polymer electrolytes containing solvate ionic liquids (SILs) with increased toughness for use in lithium secondary batteries were designed by utilizing the self-assembly of ABA-type ionomer triblock copolymer, where the A-blocks are ionomers having strong intermolecular coulombic interactions. The ABA-type triblock copolymer, poly(lithium acrylate-r-acrylic acid)-b-poly(methyl methacrylate)-b-poly(lithium acrylate-r-acrylic acid) (P(LiA-r-AA)-b-PMMA-b-P(LiA-r-AA), denoted LML), was synthesized and used as the polymer electrolytes host matrix. The fundamental properties, such as rheological, mechanical, and electrochemical properties, were explored for a binary system (ion gel) comprising LML and a hydrophobic ionic liquid. Due to the strong Li+-carboxylate interactions, the tensile fracture energy of the ion gel was greatly enhanced compared to those of conventional block copolymer electrolytes using nonionic polymers, indicating that the use of the ionomer in the A-block contributed to an enhancement in the tensile strength. Furthermore, the polymer electrolytes prepared with SILs showed good Li+-conductivity and thermal stability. Electrochemical potential window of the polymer electrolytes, revealed by voltammetry, demonstrated their oxidation stability up to 4.5V vs. Li/Li+ and reversible lithium deposition and dissolution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
After several ad hoc proposals of new 2-dimensional carbon structures, interest in their actual synthesis has begun to increase. One needs a clear orientation or criteria to describe those carbon ...structures in an appropriate way. In the present paper, we propose a systematic method for discovering new stable structures of carbon crystals with sp2-bonding using advanced mathematical methods. There are two key ideas: geometric descriptions based on curvatures, symmetries, etc. and the standard realization of crystal lattices via harmonic theory to identify stable coordinates. We apply this new method to study negatively curved carbon crystals with octahedral symmetry after Mackay–Terrones 1, and identify several new structures. The stability and electronic states of the proposed structures are investigated using first principles calculations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The status of DECIGO Sato, Shuichi; Kawamura, Seiji; Ando, Masaki ...
Journal of physics. Conference series,
05/2017, Volume:
840, Issue:
1
Journal Article
Peer reviewed
Open access
DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and ...cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present..
The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal ...junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin SOX with pembrolizumab).
This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status.
Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval CI 58.4–83.5) and 96.3% (95% CI 87.3–99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%).
SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer.
NCT03382600/JapicCTI-183829.
•This study was conducted for gastric/gastroesophageal junction (G/GEJ) cancer.•Efficacy and safety of S-1 + oxaliplatin (SOX) with pembrolizumab were assessed.•Overall response rate assessed by blinded independent central review was 72.2%.•No increase in treatment-related adverse events occurred with this combination.•First-line SOX with pembrolizumab warrants further evaluation for G/GEJ cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recently, mathematical analysis clarified that sp;{2} hybridized carbon should have a three-dimensional crystal structure (K4) which can be regarded as a twin of the sp;{3} diamond crystal. In this ...study, various physical properties of the K4 carbon crystal, especially for the electronic properties, were evaluated by first principles calculations. Although the K4 crystal is in a metastable state, a possible pressure induced structural phase transition from graphite to K4 was suggested. Twisted pi states across the Fermi level result in metallic properties in a new carbon crystal.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Aim
Hepatic edema is manifested by ascites, lower limb edema and intolerable symptoms. Some patients insufficiently respond to the conventional diuretic therapy. Therefore, a novel therapeutic option ...is required. We conducted a phase 3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated with liver cirrhosis.
Methods
In our multicenter, randomized, double‐blind, placebo‐controlled trial, liver cirrhosis patients who showed insufficient response to conventional diuretics were randomly assigned to 7‐day administration of either tolvaptan at 7.5 mg/day or placebo as an add‐on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline.
Results
Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was −0.44 kg (standard deviation SD, 1.93) in the placebo group and −1.95 kg (SD, 1.77) in the tolvaptan group (P < 0.0001). Improvement rates for lower limb edema and ascites‐related clinical symptoms were higher with tolvaptan than with placebo. Even in patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline.
Conclusion
Add‐on therapy with tolvaptan was effective for the treatment of hepatic edema and ascites‐related clinical symptoms. Furthermore, tolvaptan is expected to improve low serum sodium concentration and to exert its effect regardless of serum albumin level. Add‐on therapy with tolvaptan is therefore considered to be a novel therapeutic option for hepatic edema.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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