Ajinomoto (Japan)

In recent years, the growing attention to sustainable food production and animal welfare has positioned cultured meat technologies. A key technical requirement for implementing this approach is the development of culture media independent of fetal bovine serum (FBS). 3D organoids are composed of diverse stem and differentiated cells that replicate the structure and function of living tissues. Therefore, we hypothesized that the growth factors secreted from 3D organoids could replace the FBS. In this study, we evaluated the effects of conditioned medium prepared from organoid supernatants derived from various mouse organs, including the lung, gallbladder, spleen, kidney, and bladder, on myoblast proliferation. Among these, mouse bladder organoid-derived supernatant (MBOS) showed the most pronounced proliferative effect on C2C12 cells, a myoblast cell line. RNA sequencing and flow cytometry analyses revealed that MBOS-treated C2C12 cells upregulated cell cycle-related genes (CCNB1 and CDK1) and increased the proportion of cells in the G2/M phase. Although MBOS contained a higher concentration of insulin-like growth factor (IGF)-1 than the control medium, neutralization with IGF-1 antibody did not reduce the proliferative effect. MBOS significantly promoted the proliferation of primary bovine myoblasts, suggesting its cross-species applicability. These findings suggest that MBOS is a promising candidate for FBS-free culture media with the potential to produce cultured meat.

Endogenous and exogenous enzymes influence the sensory properties of cooked rice by acting on starch during gelatinization. This study elucidated the distinct spatial distributions of endogenous α-glucosidase (E-AG) and an exogenous version derived from Aspergillus niger (A-AG) during cooking. The E-AG, A-AG, and water distributions in rice grains were visualized. E-AG was distributed throughout the raw grain, whereas A-AG was localized around starch granules, amyloplasts, and cell walls, penetrating the grain and existing along cell walls during soaking. With A-AG, the cooking time was prolonged by approximately 1min, and the temperature rise from 85 to 100°C became more gradual. This may result from enzyme-added rice's enhanced starch hydrolysis and gelatinization, which increases endothermic reactions. The modified outer area obtained at 85-100°C reached 58±7% with A-AG and 52±5% without. Moreover, the enzyme's preservation effect appears to be related to its localization.

BackgroundConventional amblyopia treatment involves the occlusion of the fellow eye using an eye patch. However, this approach imposes a substantial psychological and physical burden on pediatric patients with amblyopia, resulting in low adherence and suboptimal visual outcomes. As responsiveness to therapy declines beyond early childhood, treatments that can enhance adherence and improve efficacy are needed. We developed a virtual reality dichoptic training app (VR app) that integrates gamification and hand-eye coordination training in pediatric patients with amblyopia.ObjectiveThis study investigated the effect of a VR app on visual acuity improvement in pediatric patients with amblyopia compared with conventional occlusion therapy using an eye patch.MethodsThis is a multicenter, open-label, prospective, randomized controlled trial that will be conducted at 3 centers in Tokyo, Japan. Pediatric patients aged 3-10 years with anisometropic, strabismic, or refractive amblyopia will be enrolled. Participants will be assigned 1:1 to a VR app group or a control group. The VR app group will use the VR app at home for 1 hour per day for 6 months. The control group will undergo conventional occlusion therapy with an eye patch for 6 months. Each group will comprise 15 participants (30 participants in total). Ophthalmologic examinations will be performed at baseline and at weeks 4, 8, 12, 16, 20, and 24. The primary endpoint will be the change in the best-corrected visual acuity in the amblyopic eye from baseline to week 12. Secondary endpoints will include changes in best-corrected visual acuity, stereopsis, and ocular deviation through week 24. We will also assess treatment adherence, defined as the ratio of the cumulative actual treatment time to the cumulative prescribed time; record adverse events, and evaluate usability in the VR app group. Longitudinal changes in outcome measures will be analyzed using a mixed-effects model.ResultsParticipant enrollment will start from January 1, 2026, to September 30, 2026. The data analysis will begin on October 1, 2026, and the results will be reported by March 31, 2027.ConclusionsThis study will clarify the effectiveness of the newly developed VR app in improving treatment outcomes and adherence among pediatric patients with amblyopia. By addressing the limitations of conventional occlusion therapy and providing a potentially more efficacious and acceptable treatment option, the VR app may enhance clinical outcomes and represent a paradigm shift in the treatment of pediatric amblyopia.

Comet research has been a high priority in solar system exploration. The last two decades have witnessed three spacecraft missions to short-period comets (Stardust / NExT, Deep Impact / EPOXI, and Rosetta) as well as tremendously increased capabilities of astronomical remote sensing facilities. The primary motivation for these extensive studies has been the need to understand comets as remnants from the protosolar nebula. These objects retain the volatiles (ices) from the cold regions in the protosolar disk, where they formed. Deciphering this cosmogonic heritage requires a strong synergy between mission findings and remote-sensing observations. Missions explore specific comets at unprecedented levels of detail that cannot be gained by other means. Whereas missions are necessarily restricted to only a few targets, remote sensing observations study comets as a population. This includes objects with a wide range of dynamical histories, nucleus sizes and shapes, gas production rates, and inner coma parent volatile compositions. This presentation is focused on the close and continually evolving synergy between missions and remote sensing near-infrared (near-IR) spectroscopic measurements of cometary volatiles. The near-IR samples a suite of molecules, such as CH4, C2H2, C2H4, C2H6, NH3, HCN, CO, OCS, H2CO, CH3OH, and CO2 (from space only). It also provides the easiest way to simultaneously measure H2O (the most abundant coma gas in most active comets) from the ground through its non-resonant fluorescence lines. In whole or in part these species are considered parent volatiles – those originally stored as ices in cometary nuclei. Abundances of isotopologues (e.g., HDO, CH3D) can be constrained in exceptionally bright comets.Previous missions to short-period comets, especially Deep Impact / EPOXI and Rosetta, demonstrated the importance of ground-based near-IR observations of parent volatiles for pre-encounter characterization, parallel spacecraft and Earth-based measurements, or follow-up astronomical studies [1-11]. Extending this synergy, the Comet Interceptor mission (targeting a long-period comet [12]) can be supported by the modern near-IR spectrographs now operating at the NASA Infrared Telescope Facility, W. M. Keck Observatory, European Southern Observatory, and Gemini. These ground-based facilities offer high spectral resolving power, allowing emission lines from different molecules to be distinguished and establishing volatile abundances with unprecedented sensitivity. Examples of particular avenues for integration with mission results include:1. Detailed compositional measurements with emphasis on relative coma abundances among species (for example, C2H2/C2H6, CO/H2CO/CH3OH, NH3/H2O, etc.).2. Spatially resolved measurements of volatile column densities and gas rotational temperatures. These are diagnostic of the physical conditions in the inner collisional coma (to which near-IR observations are most sensitive), and to the role of various dynamic and thermodynamic processes that shape the coma environment. 3. Spatial studies also provide insights into heterogeneous outgassing and the sources of volatile release – directly from the nucleus versus release from icy grains ejected into the coma. Physical coma models [13] have been developed to evaluate the contributions of both nucleus and extended sources. Previously validated against EPOXI, Rosetta, and ground-based data, these models can be applied to the vastly different spatial scales and observing geometries of spacecraft measurements versus simultaneously or contemporaneously obtained ground-based data, thereby enabling unified interpretation of both.4. As done for the EPOXI target 103P/Hartley 2 [6], a near-IR spectral survey would provide a complete inventory of all emission lines detected in the L-band. Through comparison with molecular fluorescence models and available laboratory spectra, emission lines can be identified by measured frequency, intensity, and quantum assignment, and included in a database available to both mission and ground-based researchers.In addition to providing direct mission support, telescopic near-IR measurements serve as a “bridge” between detailed findings on specific mission targets and taxonomic studies of a larger number of comets using established and uniformly implemented remote sensing techniques.

Advanced semiconductor packages have evolved through multilayering and the increased use of dielectric materials, leading to mechanical issues that affect package yield and reliability. This study evaluates the impact of interlayer dielectric materials on the mechanical reliability of package substrates. Ajinomoto Build-up Film ® (ABF) is commonly used as an interlayer dielectric material for package substrates. To enhance mechanical strength, ABF-GCP was developed, featuring a “Glass-Cloth” impregnated dielectric layer and a “Primer” for the semi-additive process (SAP). Specifically, we focused on the warpage behavior and crack propagation suppression effects of the rigid material ABF-GCP. Experiments were conducted using <tex>$60 \times 60 ~\text{mm}^{2}$</tex> package substrates with a 4-2-4 design, and the warpage behavior was measured using the shadow moiré, while the mechanical reliability was evaluated through thermal cycle tests. The results confirmed that ABF-GCP effectively suppresses the warpage during heating and the thermal degradation, as well as the crack propagation, thereby enhancing the overall reliability of the package. When stiffeners were used, it was shown that warpage behavior is dominated by the stiffeners, highlighting the importance of matching the Coefficient of Thermal Expansion (CTE) of materials. The use of ABF-GCP stabilizes the warpage behavior, allowing for more advanced implementations and greater flexibility in the component placement. These findings suggest that the appropriate placement of ABF-GCP can significantly improve the long-term durability and reliability of packages.

l-threonine is used in dietary supplements and nutritional products ingested by healthy consumers. The objective of this study was to determine in a randomized double blind controlled clinical trial the safety and tolerability of l-threonine used as graded doses in supplements for 4 weeks. Healthy male adults (age 42.9) ingested randomly placebo or different doses of L-threonine (0, 3, 6, 9, 12 g/day) for 4 weeks using a crossover design. At the end of supplementation period, the subjects visited the clinic for medical examination, anthropometric parameter measurements, blood sampling for biochemical tests including amino acid concentrations in plasma, measurement of blood pressure and heart rate, and dietary intake evaluation. Adverse events were recorded all along the trial. None of the anthropometric parameters measured, dietary intake and the biochemical parameters were affected by l-threonine supplementation except a non-specific minor increase in plasma aspartate amino transferase and creatine kinase which was measured in the group supplemented with 9 g l-threonine per day but not with the 12 g per day dose. Also, the concentration of L-threonine as well as the concentration of its metabolite L-2-amino butylate were found to be increased in plasma after supplementation with 6, 9, 12 g/day L-threonine. The moderate and mild adverse events were found to occur at random. All symptoms disappeared during the supplementation period despite continuous L-threonine supplementation. These results of this study indicate a no-observed-adverse-effect-level (NOAEL) value for L-threonine to be 12 g/day in healthy adult males. This study was registered at jRCT as jRCT1050230137.

Sequence-based protein redesign methods, such as full consensus design (FCD) and ancestral sequence reconstruction (ASR), have the potential to construct new enzymes utilizing protein sequence data registered in a rapidly expanding sequence database. The high thermostability of these enzymes would expand their application in diagnostics and molecular biology. These enzymes have also demonstrated a high level of active expression by Escherichia coli. These characteristics make these APs attractive candidates for industrial application. In addition, different amino acid residues are primarily responsible for thermal stability and active expression, suggesting important implications for strategies for designing enzymes by FCD and ASR.

Amino acids, including asparagine, aspartate, glutamine, and glutamate, play important roles in purine and pyrimidine biosynthesis as well as serve as anaplerotic sources fueling the tricarboxylic acid (TCA) cycle for mitochondrial energy generation. Despite extensive studies on glutamine and glutamate in CHO cell cultures, the roles of asparagine and aspartate, especially in feed media, remain underexplored. In this study, we utilized a CHO genome scale model to first deeply characterize the intracellular metabolic states of CHO cells cultured in different combinations of basal and feed media to understand the traits of asparagine/aspartate-dependent and glutamate-dependent feeds. Subsequently, we identified the critical role of asparagine and aspartate in the feed media as anaplerotic sources and conducted in silico simulations to ascertain their optimal ratios to improve cell culture performance. Finally, based on the model simulations, we reformulated the feed media by tailoring the concentrations of asparagine and aspartate. Our experimental data reveal a CHO cell preference for asparagine compared with aspartate, and thus maintaining an optimal ratio of these amino acids is a key factor for achieving optimal CHO cell culture performance in biopharmaceutical production.