Riso Kagaku (Japan)

Cerebellar granule cell migration plays a crucial role in cerebellum development, and any abnormalities in CGC migration can lead to significant neurological disorders such as anxiety, a common psychological disorder that impacts a person's emotional, physical, and social health. L-theanine, an amino acid found in green tea, demonstrates neuroprotective properties and regulates the release of neurotransmitters by stimulating CGC migration. This study investigated the impact of L-theanine on CGC migration related to cognitive disorders. ddY male mice treated with a single oral dose of L-theanine at varying concentrations (10 mg/kg) were assessed for anxiety, learning, and memory using the maze test and the Morris Water Maze test, where the average completion time and escape time of the mice were considered indicators of cognitive performance. CGC microexplants were isolated from newly born C57BL/N6 mice and treated with a series of increasing concentrations of L-theanine. The migration distance of the CGC under the different L-theanine concentrations was assessed after 24, 48, and 72 h post-treatment using phase-contrast microscopy and image analysis software. Mice's anxiety symptoms improved based on their performance on the maze test after treatment with L-theanine at 5 mg/ml. However, L-theanine at 0.05 mg/ml enhanced learning and memory abilities. Compared to other concentrations, L-theanine at 1 µM yielded the longest migration distance for CGC in vitro. Therefore, L-Theanine may serve as a potential therapeutic agent in supporting cerebellar development and enhancing cognitive skills. Further investigation is required to fully elucidate the molecular mechanisms and therapeutic potential of L-theanine in neurodevelopmental disorders.

Accurately predicting novel compound-protein interactions (CPIs) is essential for accelerating drug discovery. The generalizability of machine learning-based CPI prediction models relies significantly on the availability and diversity of CPI datasets. To maximize data utility, particularly for highly confidential datasets maintained by industries, federated learning (FL)—which integrates multi-site data while preserving privacy—has emerged as a promising approach. Nonetheless, its effectiveness when applied to heterogeneous data from diverse molecular domains, a common real-world scenario, remains unclear, thereby limiting its broader adoption. This study evaluates FL for CPI prediction using datasets spanning multiple chemical and protein domains, providing practical guidance for optimizing the FL approach. Results indicate that the FL model enhanced out-of-domain prediction performance but was surpassed by local models for in-domain data under data heterogeneity. Drawing on these findings, a new strategy was developed to achieve robust performance for in- and out-of-domain tasks: a similarity-guided ensemble that combines the global FL model with fine-tuned models based on each client's local data. This method demonstrated effectiveness with real-world industry data, including samples from the public database and 13 pharmaceutical companies. Cumulatively, these findings offer practical guidance for implementing FL in contemporary drug discovery processes.

To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None were currently taking XOR inhibitors. XOR activity of fasting blood samples was assayed using a stable isotope-labeled substrate and LC-TQMS. JMP Clinical version 5.0. was used for analysis. We analyzed 54 patients. Mean age was 64.7 years, mean body mass index was 26.0 kg/m2, and mean glycated hemoglobin was 9.4%. The logarithmically transformed plasma XOR activity (ln-XOR) correlated positively with hypoxanthine, xanthine, visceral fatty area, and liver dysfunction but negatively with HDL cholesterol. ln-XOR correlated negatively with diabetes duration and maximum intima-media thickness. Stepwise multiple regression analysis revealed ln-XOR to be among selected explanatory factors for various NCS parameters. Receiver operating characteristic curves showed the discriminatory power of ln-XOR. Principal component analysis revealed a negative relationship of ln-XOR with F-waves as well as positive relationships of ln-XOR with hepatic steatosis and obesity-related disorders. Taken together, our results show plasma XOR activity to be among potential disease status predictors in T2DM patients. Plasma XOR activity measurements might reliably detect pre-symptomatic DSP.

We evaluated the effects of feeding high volumes of milk replacer on growth and reproductive performances in Japanese black heifers. Fifty-one heifers were fed milk replacer at 9L/day for 60days (9L×60days; n=18) or 41days (9L×41days; n=15), or at 7L/day for 40days (7L×40days; n=18). Artificial insemination (AI) was performed on heifers with ≥270kg body weight and ≥116cm body height at 300days of age. The age at the first AI was 0.35month later for 7L×40days than the other groups (p<.01). However, age at calving did not differ among treatments (22.1months). The interval from the first AI to pregnancy tended to be ~2months longer for the 9L×60days than the other groups (p=.07). Our results showed that feeding high volumes of milk replacer may reduce the age at calving via an improved rate of growth. In addition, we propose that feeding a maximum of 7L milk replacer for 40days may be the most appropriate rearing regime because the success of pregnancy per AI may be reduced in calves fed a maximum of 9L for 41 and 60days.

Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue. The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017. Thirty-five companies based in Japan and 12 companies based in other countries, 47 companies in total, responded to the survey. The terms co-primary endpoints, secondary endpoint, and composite endpoint were used in a variety of ways. An endpoint for a clinically most important event that is expected to occur rarely differed between regions. Although the Pharmaceuticals and Medical Devices Agency did not demand multiplicity adjustment, it was considered in clinical trials with multiple endpoints for approval in Japan. The use of terminology differed from the definition in the Food and Drug Administration guidance and the European Medicines Agency guideline. There remain challenges on a clinically most important event that is expected to occur rarely and multiplicity adjustment in clinical trials with multiple endpoints.

日本では 1997 年の京都議定書から温暖化抑制に向けた取組が注目され、パリ協定の採択後は世界的な温暖化対策の取組が求められている。また事務所においても温室効果ガス排出量（GHG 排出量）が少ないことが商品購入の選択肢のひとつになっている。事務所で使用されるプリンタ、消耗品、用紙は、複数のメーカーが製造しており、其々に趣向を凝らした GHG 排出量が開示されている。またタイプⅢ環境ラベルのエコリーフは、製品分類別算定基準（PCR）で条件を定め GHG 排出量を算出するが、プリンタは様々な状況で利用されており、プリンタの利用状況毎に情報を提供することは難しい。一方、プリンタの印刷物を第三者に販売、提供する場合は、印刷物の GHG 排出量を開示した方が良いが、プリンタと用紙で提供される企業が異なることから、別々に開示されたGHG 排出量を基に、プリンタの利用者が印刷物の GHG 排出量を算出する必要がある。そこで本研究は、プリンタの利用状況に立脚した条件を基に、印刷ページあたりの GHG 排出量を定量化し、その結果、GHG 排出量を抑制する要因が明確になり、また利用者に製品選択の幅を広げた。

Research and development of SiC/SiC composite materials as structural members of aerospace engines is progressing. In order to manufacture SiC/SiC composites with excellent high-temperature characteristics, the SiC fibers which have high mechanical properties at high temperature are necessary; thus, further development of SiC fibers is considered a critical issue. In addition, the development of low-cost SiC fibers is necessary for the practical application of SiC/SiC composites. Here, the low-cost SiC fibers can be fabricated by dry spinning method. In the dry-spinning method, the raw material, Polycarbosilane (PCS) is dissolved in an organic solvent and the solution is spun at room temperature. As high-molecular-weight Polycarbosilane is prepared in advance, the infusible process conventionally required in the melt-spinning method is not required. In this study, to evaluate the differences among dry-spun SiC fibers fabricated under various conditions, monofilament tensile tests were conducted. Examination of the fracture surface and elemental analysis of arbitrary cross-sections were then performed to investigate the effects of the fabrication conditions. The tensile strength results indicated that defects were suppressed by excluding low-molecular-weight components and that heat treatment between 1300°C and 1500°C resulted in the maximum strength. Weibull analysis revealed that the dry-spun fibers exhibited lower tensile strength but smaller variation of fiber strength than that of the melt-spun fiber because the dry-spun fibers were more homogeneous. However, evaluation of the crystallinity indicated that the interference pattern derived from the crystal was unclear in the dry-spun fibers but clear in the melt-spun fiber. Therefore, it was suggested that the dry-spun fibers exhibited lower crystallinity than the melt-spun fiber. In addition, the dry-spun and melt-spun fibers exhibited similar C/Si ratios, whereas a large amount of oxygen was detected on the surface of the dry-spun fiber relative to that on the surface of the melt-spun fiber. Further improvement of the mechanical properties is expected upon increasing the molecular weight of the raw material and improving the microstructure.

オーツ麦（Avena stativa L.）は，昔から食用の穀物としてだけでなく，その水分散体がさまざまな乾燥性の皮膚疾患に伴う痒みや刺激性を和らげるものとして使われてきた。本来，オーツ麦には天然のフィトケミカルが豊富に存在し，フェノール性化合物やフラボノイドには抗酸化作用や抗炎症効果が，多糖類成分には保湿効果が期待できる。オーツ麦から製造した微粉砕粉は，コロイダルオートミール（COM）と呼ばれ，化粧品原料として使われている。本研究では，脱殻後，微粉砕前に湿熱処理の1つであるエクストルーダー処理を行い製造したコロイダルオートミール（ExtCOM）と従来のCOMの性質について比較検証した。その結果，ExtCOMは粒度分布プロファイルがCOMとまったく異なり，β-グルカンの溶出量や抗酸化能が従来のCOMに比べて非常に高いことがわかった。さらに，比表面積と抗酸化能の関係性という観点でデータを分析し，エクストルーダー処理による穀物細胞構造の物理化学的変化がフィトケミカルの生物学的利用能の向上に大きく寄与している可能性があると結論づけた。

Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.