Introduction and Objective: Oxidative stress and mitochondrial dysfunction play a pivotal role in the pathogenesis of diabetic neuropathy. We previously reported that hyperglycemia and glucose fluctuations induce mitochondrial dysfunction and cell death in immortalized adult mouse Schwann (IMS32) cells. Recently, the oral glucose-lowering drug imeglimin has been shown to attenuate ROS generation and improve mitochondrial function in hepatocytes. In addition, nicotinamide mononucleotide (NMN), a precursor of NAD+, has emerged as a key regulator of energy metabolism and cellular senescence. In this study, we investigated the effects of imeglimin and NMN on high glucose-induced mitochondrial dysfunction and cellular senescence in Schwann cells. Methods: IMS32 cells were cultured under either normal glucose (5.5 mM) or high glucose (25 mM). The levels of mitochondrial oxidative stress and intracellular NAD+ were measured. The protein expression levels of the longevity gene Sirt1 and the mitochondrial biogenesis-related factors PGC1α and TFAM were evaluated. Senescent cells were identified by senescence-associated β-galactosidase (SA-β-gal) staining. Results: Imeglimin and NMN suppressed high glucose-increases in mitochondrial oxidative stress. Imeglimin significantly increased intracellular NAD+ levels. Both agents restored the high glucose-induced downregulation of Sirt1, PGC1α, and TFAM expression and attenuated the increase in SA-β-gal-positive cells. Conclusion: These findings suggest that the accumulation of senescent Schwann cells may contribute to the development and progression of diabetic neuropathy. Imeglimin and NMN improved high glucose-induced mitochondrial dysfunction and suppressed cellular senescence in Schwann cells, suggesting its potential therapeutic benefits for diabetic neuropathy. Disclosure A. Kato: None. W. Nihei: None. H. Yako: None. N. Nakamura: None. K. Naruse: None. T. Himeno: None. Y. Kato: None. J. Nakamura: None. H. Kamiya: Research Support; Current; Boehringer Ingelheim International GmbH, CBC, Daiichi Sankyo, EA Pharma, Eli Lilly and Company, Fukuda Denshi, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., MSD, Mochida Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Parexel International, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Current; Abbott Japan Co., Ltd., Array BioPharma Inc., Astellas Pharma Inc., AstraZeneca, Bayer AG, Chugai Pharmaceutical Co., Ltd., EA Pharma, Eli Lilly and Company, Eisai Inc., Fukuda Denshi, GlaxoSmithKline plc., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Novartis Pharma K.K., Novo Nordisk, Mitsubishi Tanabe Pharma Corporation, MSD, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Sanwa Kagaku Kenkyusho, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Viatris Inc. K. Sango: None. K. Kato: Speaker's Bureau; Current; Daiichi Sankyo.
This paper presents the DECICE project (Device Edge Cloud Intelligent Collaboration framEwork), a Horizon Europe Research and Innovation Action (Grant No. 101092582, December 2022 to November 2025) that developed an open-source framework for intelligent workload scheduling across the cloud-HPC-edge compute continuum. A consortium of 12 partners across 6 European countries organized the work into six work packages covering AI-driven scheduling, digital twin infrastructure, system architecture and integration, monitoring, use case validation, and dissemination. The two core technical contributions are an Integrated AI Scheduler (IAIS) employing RNN-based prediction and formal workflow modeling for constraint-aware workload mapping, and a Digital Twin aggregating real-time metrics with carbon intensity and anomaly prediction for energy-aware scheduling. The framework operates within Kubernetes environments, supports unified workflow ingestion from multiple formats, and bridges cloud-native and HPC orchestration through a Slurm integration layer. We present the project vision, the overall architecture, contributions from each work package, quantitative evaluation results, and the open-source release.
Reaction models are essential for understanding chemical reactions, but modeling them is a time-demanding process. Automated reaction space exploration techniques, such as ChemTraYzer-TAD, can simplify this process. However, finding transition states (TS) remains a hurdle. TS geometries are crucial for calculating reaction rate constants. Quantum mechanical methods are computationally expensive for TS geometry searches, while reactive molecular mechanics, like ReaxFF, offer faster calculations. Accurate TS searches require second derivatives of energy. State-of-the-art ReaxFF implementations can provide these derivatives only through finite differentiation (FD), which introduces noise. Automatic differentiation (AD) can provide more accurate second derivatives. Hence, this work integrates AD into the classical molecular dynamics code LAMMPS for calculations of second derivatives, presenting ADfied LAMMPS. By interfacing ADfied LAMMPS with the Gaussian computational chemistry suite, LMP-Gau is developed, enabling efficient geometry optimization, frequency calculations, and reaction path following for any force field. LMP-Gau demonstrates improved energy minimization for stable molecules in comparison to standard LAMMPS methods. It is also used successfully to find transition states in 1,3-dioxolane oxidation, demonstrating improved convergence with AD compared to FD.
CDs and DVDs are a type of electronic plastic waste (EPW) and pose an environmental burden owing to their low biodegradability and the absence of viable large-scale strategies for their disposal. Using EPW as replacement components in construction materials, such as concrete and mortar, offers an alternative, sustainable solution to this problem. Moreover, the paper focused on the feasibility of substituting ordinary Portland cement with waste supplementary cementing materials, namely fly ash (FA) and silica fume (SF). The aim is to find environmentally friendly and economical applications of the FA. This study investigates the physical and mechanical properties of lightweight mortar specimens with varying EPW contents to optimise their composition for practical implementation in construction materials. Water absorption, ultrasonic pulse velocity (UPV), bulk density, compressive strength, and flexural strength were measured at 7, 28, and 90 days. The results demonstrate the potential to produce sustainable, lightweight mortar from EPW and that replacing 50
Introduction and Objective: Imeglimin is a novel antidiabetic agent that enhances mitochondrial function, promoting insulin secretion and improving glucose metabolism in liver and skeletal muscle. Despite its clinical use in Japan, real-world evidence on its efficacy across ages and its broader metabolic effects in type 2 diabetes mellitus (T2DM) remains limited. We evaluated the efficacy and safety of imeglimin and assessed whether patient age influences treatment effects. Methods: Fifty-two Japanese outpatients with T2DM received imeglimin 1,000 mg twice daily for three months. Pre- and post-treatment assessments included HbA1c, body weight, BMI, lipid profile, hepatic enzymes, renal markers, uric acid, and amylase. Results: Imeglimin significantly reduced body weight, BMI, and HbA1c from baseline. Lipid parameters improved, with decreases in total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, along with a more favorable atherogenic profile. Hepatic enzymes (AST, ALT, γ-GTP) declined, indicating improvement in liver-related parameters. Renal indices (BUN, creatinine, eGFR) and amylase showed no clinically relevant changes, supporting a favorable safety profile; uric acid showed no overall change. The magnitude of reductions in hepatic enzymes and uric acid varied with age and baseline values, whereas the primary glycemic outcome (HbA1c reduction) was not influenced by age, suggesting consistent glycemic benefits across a wide range of age. Conclusion: Three months of imeglimin therapy improved glycemic control and favorably modified weight, lipid profile, and hepatic enzymes in Japanese patients with T2DM, without adverse effect in the kidney. HbA1c reduction was age-independent, indicating that imeglimin provides reliable glycemic improvement from younger to older adults and may be particularly useful when lifestyle interventions are difficult to implement. These findings support imeglimin as a safe, effective option for comprehensive metabolic management in routine care. Disclosure M. Kusunoki: None. F. Hisano: None. S. Matsuda: None. T. Miyata: None.
