pH-Responsive Self-Assembly of Designer Aromatic Peptide Amphiphiles and Enzymatic Post-Modification of Assembled Structures

Supramolecular fibrous materials in biological systems play important structural and functional roles, and therefore, there is a growing interest in synthetic materials that mimic such fibrils, especially those bearing enzymatic reactivity. In this study, we investigated the self-assembly and enzymatic post-modification of short aromatic peptide amphiphiles (PAs), Fmoc-L_nQG (n = 2 or 3), which contain an LQG recognition unit for microbial transglutaminase (MTG). These aromatic PAs self-assemble into fibrous structures via π-π stacking interactions between the Fmoc groups and hydrogen bonds between the peptides. The intermolecular interactions and morphologies of the assemblies were influenced by the solution pH because of the change in the ionization states of the C-terminal carboxy group of the peptides. Moreover, MTG-catalyzed post-modification of a small fluorescent molecule bearing an amine group also showed pH dependency, where the enzymatic reaction rate was increased at higher pH, which may be because of the higher nucleophilicity of the amine group and the electrostatic interaction between MTG and the self-assembled Fmoc-L_nQG. Finally, the accumulation of the fluorescent molecule on these assembled materials was directly observed by confocal fluorescence images. Our study provides a method to accumulate functional molecules on supramolecular structures enzymatically with the morphology control.     

Cardiovascular Outcomes in the Acute Phase of COVID-19

The cumulative number of cases in the current global coronavirus disease 19 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exceeded 100 million, with the number of deaths caused by the infection having exceeded 2.5 million. Recent reports from most frontline researchers have revealed that SARS-CoV-2 can also cause fatal non-respiratory conditions, such as fatal cardiovascular events. One of the important mechanisms underlying the multiple organ damage that is now known to occur during the acute phase of SARS-CoV-2 infection is impairment of vascular function associated with inhibition of angiotensin-converting enzyme 2. To manage the risk of vascular dysfunction-related complications in patients with COVID-19, it would be pivotal to clearly elucidate the precise mechanisms by which SARS-CoV-2 infects endothelial cells to cause vascular dysfunction. In this review, we summarize the current state of knowledge about the mechanisms involved in the development of vascular dysfunction in the acute phase of COVID-19.     

Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.     

Role of Glycated High Mobility Group Box-1 in Gastric Cancer

Advanced glycation end products (AGEs) are produced in response to a high-glucose environment and oxidative stress and exacerbate various diseases. N^ε-(Carboxymethyl)lysine (CML) is an AGE that is produced by the glycation of lysine residues of proteins. There are a few reports on alterations in protein function due to CML modification; however, its association with cancer is not clear. We investigated the significance of CML modification in high mobility group box protein-1 (HMGB1), a cytokine that is significantly associated with cancer progression. Treatment of the gastric cancer cell lines TMK1 and MKN74 with glyoxal or glucose resulted in increased CML modification compared to untreated cells. CML-HMGB1 was modified via oxidation and more pronouncedly activated the receptor for AGE and downstream AKT and NF-κB compared to naïve HMGB1 and oxidized HMGB1. CML-HMGB1 bound with reduced affinity to DNA and histone H3, resulting in enhanced extranuclear translocation and extracellular secretion. Treatment of gastric cancer cells with CML-HMGB1 enhanced cell proliferation and invasion, sphere formation, and protection from thapsigargin-induced apoptosis, and decreased 5-FU sensitivity in comparison to HMGB1. Further, CML-HMGB1 was detected at various levels in all the 10 gastric cancer tumor specimens. HMGB1 levels correlated with primary tumor progression and distant metastasis, whereas CML-HMGB1 levels were associated with primary tumor progression, lymph node metastasis, distant metastasis, and stage. In addition, CML-HMGB1 levels correlated with oxidative stress in cancer tissues and resistance to neoadjuvant therapy. Therefore, CML modification of HMGB1 enhanced the cancer-promoting effect of HMGB1. In this study, CML-HMGB1 has been highlighted as a new therapeutic target, and analysis of the molecular structure of CML-HMGB1 is desired in the future.     

Hydrogen production using thermochemical water-splitting Iodine–Sulfur process test facility made of industrial structural materials: Engineering solutions to prevent iodine precipitation

A thermochemical water-splitting iodine–sulfur process offers the potential for mass-producing hydrogen at high-efficiency levels, and it uses high-temperature heat sources, including high-temperature gas-cooled reactors, solar heat, and waste heat of industries. The raw material (H₂O) is split into H₂ and O₂ by combining three chemical reactions using sulfur and iodine. Currently, R&D tasks are essential to confirm the integrity of the components that are made of practical structural materials and the stability of hydrogen production in harsh working conditions. A test facility for producing hydrogen was constructed from corrosion-resistant components that are developed using industrial materials. In addition, for stable hydrogen production, technical issues for instrumental improvements (i.e., stable pumping of the hydrogen iodide (HI)–I₂–H₂O solution without locking the shaft seal, prevention of leakage by improving the quality control of glass-lined steel, prevention of I₂ precipitation using a water removal technique in a Bunsen reactor) were solved. The entire process was successfully operated for 150 h at the rate of ca. 30 L/h. The integrity of components made of practical structural materials and the operational stability of the hydrogen production facility in harsh working conditions were demonstrated.     

The Mechanisms Underlying Autonomous Adrenocorticotropic Hormone Secretion in Cushing’s Disease

Cushing’s disease caused due to adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (ACTHomas) leads to hypercortisolemia, resulting in increased morbidity and mortality. Autonomous ACTH secretion is attributed to the impaired glucocorticoid negative feedback (glucocorticoid resistance) response. Interestingly, other conditions, such as ectopic ACTH syndrome (EAS) and non-neoplastic hypercortisolemia (NNH, also known as pseudo-Cushing’s syndrome) also exhibit glucocorticoid resistance. Therefore, to differentiate between these conditions, several dynamic tests, including those with desmopressin (DDAVP), corticotrophin-releasing hormone (CRH), and Dex/CRH have been developed. In normal pituitary corticotrophs, ACTH synthesis and secretion are regulated mainly by CRH and glucocorticoids, which are the ACTH secretion-stimulating and -suppressing factors, respectively. These factors regulate ACTH synthesis and secretion through genomic and non-genomic mechanisms. Conversely, glucocorticoid negative feedback is impaired in ACTHomas, which could be due to the overexpression of 11β-HSD2, HSP90, or TR4, or loss of expression of CABLES1 or nuclear BRG1 proteins. Genetic analysis has indicated the involvement of several genes in the etiology of ACTHomas, including USP8, USP48, BRAF, and TP53. However, the association between glucocorticoid resistance and these genes remains unclear. Here, we review the clinical aspects and molecular mechanisms of ACTHomas and compare them to those of other related conditions.     

Improvement of Abnormality Detection System for Bathers Using Ultrasonic Sensors

This paper proposes a new method for improving an existing abnormality detection system for a person who soaks in a bathtub. As the number of aged people increases year by year in Japan, bathing accidents among the aged are growing at a rapid rate, especially in‐bathtub drowning accidents. Therefore, prompt detection of a bather's abnormality, such as dizziness and fainting, is important to prevent in‐bathtub drowning. In order to detect a bather's abnormality promptly, an abnormality detection system using seven ultrasonic sensors has been proposed. The system uses two methods—posture detection and motion detection—to detect a difference in a bather's state compared to normal before an accident occurs, and improves the delay in detection considered heretofore to be a serious problem. There was, however, plenty of room for improvement. In order to improve the detection rate of the system, we propose a new detection method in this paper. The method uses two ultrasonic sensors to scan a bather's head and neck, and detects the head height and swing speed of the head. Experimental results are superior to the accuracy of the existing system, which enables us to detect an abnormality in a bather more precisely. © 2012 Wiley Periodicals, Inc. Electr Eng Jpn, 179(3): 57–67, 2012; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.21133     

Genetic Algorithm Optimization for Tensioning in a Rotating Circular Saw Under a Thermal Load

The optimization problem for tensioning conditions in a rotating circular saw under a thermal load is solved by a genetic algorithm. The governing equations for the in-plane behavior due to rotation, thermal load by friction, and plastic strain by tensioning and those for the resulting out-of-plane behavior are presented; the solution for in-plane forces is obtained; and a modal analysis is performed. Numerical calculations are performed to investigate the effect of tensioning conditions on the natural frequencies. The optimization problem to maximize the natural frequency of the most critical mode is solved, and the optimal tensioning conditions are determined.