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Bridging the gap between scientific knowledge and practical application remains a central challenge in research and development (R&D). Analytical R&D generates factual knowledge through established methodologies, whereas synthetic R&D integrates this knowledge with technological and practical insights to produce artifacts and solutions. Despite its importance, synthetic R&D has lacked a coherent methodological foundation, limiting its broader recognition and systematic practice. We develop and demonstrate a scenario-based methodology that provides a structured framework for synthetic R&D. A scenario is defined as a development pathway that systematically links scientific understanding to clearly defined application objectives. By defining internal and external scenario structures, the framework enables systematic planning, execution, and evaluation of projects. Scenarios also serve as boundary objects, facilitating collaboration and communication across different disciplines and organizations. The originality of this study lies in transforming previously implicit or fragmented practices into a systematic, reproducible, and evaluable process. The methodology is validated through empirical case studies: nanomaterials standardization, deployment of ear thermometers during public health emergencies, and geochemical mapping for environmental policy. These cases illustrate how structured scenarios support knowledge integration, enhance adaptability across technical domains, and generate outcomes with demonstrable industrial and societal value. These findings suggest that scenario-based approaches provide a robust, generalizable foundation for advancing synthetic R&D in parallel with analytical R&D.

A coherent standardization framework is essential for the industrial deployment of cellulose nanomaterials (CNMs). Although CNMs offer attractive properties for diverse industrial applications, their distinct morphological types—cellulose nanocrystals (CNCs), individualized cellulose nanofibrils (iCNFs), and entangled cellulose nanofibrils (eCNFs)—introduce morphological complexity that hinders reproducible quality evaluation. ISO has established terminology and several test method standards; however, testing standards remain limited for CNCs and iCNFs, and are still lacking for eCNFs, leaving a significant gap between material characterization and industrial use. This study proposes a structured framework that aligns terminology, test method, testing, and specification standards along the CNM industrialization pathway. The framework highlights the essential role of testing standards as the appropriate evaluation basis for CNMs at their present developmental stage, in contrast to specification standards suited to mature materials with clearly defined applications. A complementary scenario-based methodology is also introduced to support coherent and reproducible development of individual testing standards. By positioning existing ISO CNM standards within this pathway and clarifying the evaluative and bridging functions of testing standards, this study provides an industry-oriented foundation for reliable CNM quality assessment. The conceptual approach may also support standardization strategies for other bio-based materials in similarly early stages of industrialization.

HIV-1 viral particle assembly occurs specifically at the plasma membrane and is driven primarily by the viral polyprotein Gag. Selective association of Gag with the plasma membrane is a key step in the viral assembly pathway, which is traditionally attributed to the MA domain. MA regulates specific plasma membrane binding through two primary mechanisms including: (1) specific interaction of the MA highly basic region (HBR) with the plasma membrane phospholipid phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2], and (2) tRNA binding to the MA HBR, which prevents Gag association with non-PI(4,5)P2 containing membranes. Gag multimerization, driven by both CA–CA inter-protein interactions and NC-RNA binding, also plays an essential role in viral particle assembly, mediating the establishment and growth of the immature Gag lattice on the plasma membrane. In addition to these functions, the multimerization of HIV-1 Gag has also been demonstrated to enhance its membrane binding activity through the MA domain. This review provides an overview of the mechanisms regulating Gag membrane binding through the MA domain and multimerization through the CA and NC domains, and examines how these two functions are intertwined, allowing for multimerization mediated enhancement of Gag membrane binding.

Influenza A Virus (IAV) is a respiratory virus that causes seasonal outbreaks annually and pandemics occasionally. The main targets of the virus are epithelial cells in the respiratory tract. Like many other viruses, IAV employs the host cell’s machinery to enter cells, synthesize new genomes and viral proteins, and assemble new virus particles. The cytoskeletal system is a major cellular machinery, which IAV exploits for its entry to and exit from the cell. However, in some cases, the cytoskeleton has a negative impact on efficient IAV growth. In this review, we highlight the role of cytoskeletal elements in cellular processes that are utilized by IAV in the host cell. We further provide an in-depth summary of the current literature on the roles the cytoskeleton plays in regulating specific steps during the assembly of progeny IAV particles.

Nascent HIV-1 particles incorporate the viral envelope glycoprotein and multiple host transmembrane proteins during assembly at the plasma membrane. At least some of these host transmembrane proteins on the surface of virions are reported as pro-viral factors that enhance virus attachment to target cells or facilitate trans-infection of CD4+ T cells via interactions with non-T cells. In addition to the pro-viral factors, anti-viral transmembrane proteins are incorporated into progeny virions. These virion-incorporated transmembrane proteins inhibit HIV-1 entry at the point of attachment and fusion. In infected polarized CD4+ T cells, HIV-1 Gag localizes to a rear-end protrusion known as the uropod. Regardless of cell polarization, Gag colocalizes with and promotes the virion incorporation of a subset of uropod-directed host transmembrane proteins, including CD162, CD43, and CD44. Until recently, the functions of these virion-incorporated proteins had not been clear. Here, we review the recent findings about the roles played by virion-incorporated CD162, CD43, and CD44 in HIV-1 spread to CD4+ T cells.

Membrane binding of Gag, a crucial step in HIV-1 assembly, is facilitated by bipartite signals within the matrix (MA) domain: N-terminal myristoyl moiety and the highly basic region (HBR). We and others have shown that Gag interacts with a plasma-membrane-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P₂], via the HBR, and that this interaction is important for efficient membrane binding and plasma membrane targeting of Gag. Generally, in protein-PI(4,5)P₂ interactions, basic residues promote the interaction as docking sites for the acidic headgroup of the lipid. In this study, toward better understanding of the Gag-PI(4,5)P₂ interaction, we sought to determine the roles played by all of the basic residues in the HBR. We identified three basic residues promoting PI(4,5)P₂-dependent Gag-membrane binding. Unexpectedly, two other HBR residues, Lys25 and Lys26, suppress membrane binding in the absence of PI(4,5)P₂ and prevent promiscuous intracellular localization of Gag. This inhibition of nonspecific membrane binding is likely through suppression of myristate-dependent hydrophobic interaction because mutating Lys25 and Lys26 enhances binding of Gag with neutral-charged liposomes. These residues were reported to bind RNA. Importantly, we found that RNA also negatively regulates Gag membrane binding. In the absence but not presence of PI(4,5)P₂, RNA bound to MA HBR abolishes Gag-liposome binding. Altogether, these data indicate that the HBR is unique among basic phosphoinositide-binding domains, because it integrates three regulatory components, PI(4,5)P₂, myristate, and RNA, to ensure plasma membrane specificity for particle assembly.

Objectives We investigated the relationship between lead in air (Pb‐A) measured by personal sampling and blood lead (Pb‐B) in workers with relatively low lead exposure to estimate the permissible air concentration of lead corresponding to the biological tolerance value of Pb‐B of 15 µg/dL. Methods We collected air samples at a lead‐acid battery factory in Japan by personal sampling devices attached to 32 workers (19 males and 13 females) and measured Pb‐A by a graphite furnace atomic absorption spectrophotometer in 2017‐2020. In addition, we collected information on age, smoking habits, Pb‐B, and urinary δ‐aminolevulinic acid from the records of medical examinations for lead poisoning. Samples were collected two times from four workers, resulting in 36 data sets. Results Before analyses, we excluded four inappropriate data sets. The levels of Pb‐A in the factory and Pb‐B in the workers were almost under the current permissible limits. Multiple regression models showed significant correlations between Pb‐B and Pb‐A, and sex, and borderline significance between Pb‐B and age. Based on them, we calculated Pb‐A corresponding to Pb‐B 15 μg/dL, and obtained similar values to the current occupational exposure limit (OEL) of 30 μg/m3, with slight variation between sex and age. Conclusion These results validate OEL, although supplementary conditions in terms of sex and age may be necessary.

Enveloped viruses rely on host membranes for trafficking and assembly. A substantial body of literature published over the years supports the involvement of cellular membrane lipids in the enveloped virus assembly processes. In particular, the knowledge regarding the relationship between viral structural proteins and acidic phospholipids has been steadily increasing in recent years. In this review, we will briefly review the cellular functions of plasma membrane-associated acidic phospholipids and the mechanisms that regulate their local distribution within this membrane. We will then explore the interplay between viruses and the plasma membrane acidic phospholipids in the context of the assembly process for two enveloped viruses, the influenza A virus (IAV) and the human immunodeficiency virus type 1 (HIV-1). Among the proteins encoded by these viruses, three viral structural proteins, IAV hemagglutinin (HA), IAV matrix protein-1 (M1), and HIV-1 Gag protein, are known to interact with acidic phospholipids, phosphatidylserine and/or phosphatidylinositol (4,5)-bisphosphate. These interactions regulate the localization of the viral proteins to and/or within the plasma membrane and likely facilitate the clustering of the proteins. On the other hand, these viral proteins, via their ability to multimerize, can also alter the distribution of the lipids and may induce acidic-lipid-enriched membrane domains. We will discuss the potential significance of these interactions in the virus assembly process and the property of the progeny virions. Finally, we will outline key outstanding questions that need to be answered for a better understanding of the relationships between enveloped virus assembly and acidic phospholipids.

Objectives The present study investigated the quantitative relationship between blood lead (Pb‐B) and urinary δ⁻aminolevulinic acid (ALA‐U) in lead workers, and examined the Pb‐B level that induces increases in ALA‐U and the corresponding ALA‐U. Methods We collected 10 562 data sets on Pb‐B, ALA‐U, age, and smoking habits from 808 workers (771 males and 37 females) who underwent multiple lead poisoning medical examinations at a lead‐acid battery and lead smelting plant in Japan between 1995 and 2018. Females were excluded, and data collected in 169 subjects prior to engaging in lead work were used as the control. Pb‐B and ALA‐U levels were measured by graphite furnace atomic absorption spectrophotometry and high‐performance liquid chromatography respectively. Results A significant dose‐response relationship was observed between Pb‐B and ALA‐U based on Pb‐B‐classified observations of increases in ALA‐U values and the prevalence of over‐reference ALA‐U as well as regression analyses independent of smoking habits. The results obtained revealed that the threshold of Pb‐B to increase ALA‐U was 25.1‐35.0 µg/dL based on the significant elevation point of the prevalence of over‐reference ALA‐U and 16.2‐22.3 µg/dL from a 3rd degree regression equation. Conclusions We proposed a threshold of Pb‐B to increase ALA‐U of 20 µg/dL and a biologically acceptable value of ALA‐U of 1 mg/L, corresponding to the threshold.