Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan

The dystrophin–glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as cytidine 5′-diphosphate-glycerol (CDP-Gro) synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification.     

Role of Mitochondrial Dynamics in Cocaine’s Neurotoxicity

The dynamic balance of mitochondrial fission and fusion maintains mitochondrial homeostasis and optimal function. It is indispensable for cells such as neurons, which rely on the finely tuned mitochondria to carry out their normal physiological activities. The potent psychostimulant cocaine impairs mitochondria as one way it exerts its neurotoxicity, wherein the disturbances in mitochondrial dynamics have been suggested to play an essential role. In this review, we summarize the neurotoxicity of cocaine and the role of mitochondrial dynamics in cellular physiology. Subsequently, we introduce current findings that link disturbed neuronal mitochondrial dynamics with cocaine exposure. Finally, the possible role and potential therapeutic value of mitochondrial dynamics in cocaine neurotoxicity are discussed.     

Osteoimmunology in Periodontitis: Local Proteins and Compounds to Alleviate Periodontitis

Periodontitis is one of the most common oral diseases resulting in gingival inflammation and tooth loss. Growing evidence indicates that it results from dysbiosis of the oral microbiome, which interferes with the host immune system, leading to bone destruction. Immune cells activate periodontal ligament cells to express the receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) and promote osteoclast activity. Osteocytes have active roles in periodontitis progression in the bone matrix. Local proteins are involved in bone regeneration through functional immunological plasticity. Here, we discuss the current knowledge of cellular and molecular mechanisms in periodontitis, the roles of local proteins, and promising synthetic compounds generating a periodontal regeneration effect. It is anticipated that this may lead to a better perception of periodontitis pathophysiology.     

Software reliability measurement in imperfect debugging environment and its application

In practice, debugging operations during the testing phase of software development are not always performed perfectly. In other words, not all the software faults detected are corrected and removed. Generally, this is called imperfect debugging. In this paper, we discuss a software reliability growth model considering imperfect debugging. Defining a random variable representing the cumulative number of faults corrected up to a specified testing time, this model is described by a semi-Markov process. Then, several quantitative measures are derived for software reliability assessment in an imperfect debugging environment. The application of this model to optimal software release problems is also discussed. Finally, numerical illustrations for software reliability measurement and optimal software release policies are presented.     

Clinical Implications and Molecular Characterization of Drebrin-Positive,Tumor-Infiltrating Exhausted T Cells in Lung Cancer

T cells express an actin-binding protein, drebrin, which is recruited to the contact site between the T cells and antigen-presenting cells during the formation of immunological synapses. However, little is known about the clinical implications of drebrin-expressing, tumor-infiltrating lymphocytes (TILs). To address this issue, we evaluated 34 surgical specimens of pathological stage I–IIIA squamous cell lung cancer. The immune context of primary tumors was investigated using fluorescent multiplex immunohistochemistry. The high-speed scanning of whole-slide images was performed, and the tissue localization of TILs in the tumor cell nest and surrounding stroma was automatically profiled and quantified. Drebrin-expressing T cells were characterized using drebrin⁺ T cells induced in vitro and publicly available single-cell RNA sequence (scRNA-seq) database. Survival analysis using the propensity scores revealed that a high infiltration of drebrin⁺ TILs within the tumor cell nest was independently associated with short relapse-free survival and overall survival. Drebrin⁺ T cells induced in vitro co-expressed multiple exhaustion-associated molecules. The scRNA-seq analyses confirmed that the exhausted tumor-infiltrating CD8⁺ T cells specifically expressed drebrin. Our study suggests that drebrin-expressing T cells present an exhausted phenotype and that tumor-infiltrating drebrin⁺ T cells affect clinical outcomes in patients with resectable squamous cell lung cancer.     

Evaluation of Plant Ceramide Species-Induced Exosome Release from Neuronal Cells and Exosome Loading Using Deuterium Chemistry

The extracellular accumulation of aggregated amyloid-β (Aβ) in the brain leads to the early pathology of Alzheimer’s disease (AD). The administration of exogenous plant-type ceramides into AD model mice can promote the release of neuronal exosomes, a subtype of extracellular vesicles, that can mediate Aβ clearance. In vitro studies showed that the length of fatty acids in mammalian-type ceramides is crucial for promoting neuronal exosome release. Therefore, investigating the structures of plant ceramides is important for evaluating the potential in releasing exosomes to remove Aβ. In this study, we assessed plant ceramide species with D-erythro-(4E,8Z)-sphingadienine and D-erythro-(8Z)-phytosphingenine as sphingoid bases that differ from mammalian-type species. Some plant ceramides were more effective than mammalian ceramides at stimulating exosome release. In addition, using deuterium chemistry-based lipidomics, most exogenous plant ceramides were confirmed to be derived from exosomes. These results suggest that the ceramide-dependent upregulation of exosome release may promote the release of exogenous ceramides from cells, and plant ceramides with long-chain fatty acids can effectively release neuronal exosomes and prevent AD pathology.     

洋麻增强复合材料的开发和应用

洋麻以其价廉质轻、纤维拉伸强度高和产量高等特性而广泛应用于各种环保领域。文中综述了近年来洋麻增强复合材料的研究开发,介绍了洋麻秆芯和其韧皮纤维增强复合材料的制备成型方法、力学性能和应用,并展望了该类复合材料的未来发展趋势。     

The Stibium Bond or the Antimony-Centered Pnictogen Bond: The Covalently Bound Antimony Atom in Molecular Entities in Crystal Lattices as a Pnictogen Bond Donor

A stibium bond, i.e., a non-covalent interaction formed by covalently or coordinately bound antimony, occurs in chemical systems when there is evidence of a net attractive interaction between the electrophilic region associated with an antimony atom and a nucleophile in another, or the same molecular entity. This is a pnictogen bond and are likely formed by the elements of the pnictogen family, Group 15, of the periodic table, and is an inter- or intra-molecular non-covalent interaction. This overview describes a set of illustrative crystal systems that were stabilized (at least partially) by means of stibium bonds, together with other non-covalent interactions (such as hydrogen bonds and halogen bonds), retrieved from either the Cambridge Structure Database (CSD) or the Inorganic Crystal Structure Database (ICSD). We demonstrate that these databases contain hundreds of crystal structures of various dimensions in which covalently or coordinately bound antimony atoms in molecular entities feature positive sites that productively interact with various Lewis bases containing O, N, F, Cl, Br, and I atoms in the same or different molecular entities, leading to the formation of stibium bonds, and hence, being partially responsible for the stability of the crystals. The geometric features, pro-molecular charge density isosurface topologies, and extrema of the molecular electrostatic potential model were collectively examined in some instances to illustrate the presence of Sb-centered pnictogen bonding in the representative crystal systems considered.     

{332}<113> detwinning in a multilayered bcc-Ti–10Mo–Fe alloy

We have studied {332}<113> detwinning mechanism in a bcc-Ti–10Mo–xFe (x = 1–3 wt%) multilayered alloy upon annealing treatment at 900 °C by electron backscatter diffraction and electron channeling contrast imaging. Our analysis reveals that in the present material the detwinning process consists of two independent detwinning events that occur at two different microstructural regions, namely twin tips located at grain interiors and grain boundaries. Boundary dissociation reactions and mobilities were analyzed by tracking the evolution of the twin structure upon thermal annealing. We find that the first detwinning process is characterized by the evolution of incoherent twin boundaries into a Σ3 boundary and its subsequent migration. The second detwinning event is characterized by the detachment of the twin crystal from a grain boundary by the formation and migration of Σ11 {113} incoherent twin boundaries. Both detwinning modes can be explained from a thermodynamic standpoint where the boundary dissociation processes minimize the boundary free energy.     

In-situ evaluation for activated concrete in accelerator facility with scintillation-type gamma-ray spectrometer

The assessment of activated concrete is particularly difficult during the decommissioning of an accelerator facility.Destructive analysis by core boring is the only method of investigating the activity of concrete material.To address this problem,an in-situ and nondestructive analysis method was developed to determine γ-ray-emitting nuclides and their specific activities in the concrete walls and floor by using a portable germanium semiconductor detector.In this work,we examined a substitute for...