A versatile entry to unnatural, disulfide-linked amino acids and peptides through the disulfuration of azlactones.

Despite the evident demand and promising potential of disulfide-functionalized amino acids and peptides in linker chemistry and peptide drug discovery, those disulfurated specifically at the α-position constitute a unique yet rather highly underexplored chemical space. In this study, we have developed a method for preparing -linked amino acid/peptide derivatives through a base-catalyzed disulfuration reaction of azlactones, followed by the ring-opening functionalization. The disulfuration reaction proceeds under mild conditions, yielding disulfurated azlactones in excellent yields across a variety of -dithiophthalimides and diverse azlactones derived from various amino acids and peptides.

Inhibition of skin fibrosis via regulation of Th17/Treg imbalance in systemic sclerosis.

Systemic sclerosis (SSc) is an idiopathic systemic connective tissue disorder characterized by fibrosis of the skin and internal organs, with growing interest in the imbalance between Th17 cells and regulatory T cells (Tregs) in the disease's pathogenesis. Heligmosomoides polygyrus (Hp), a natural intestinal parasite of mice, is known to induce Tregs in the host. We aimed to investigate the effects of Hp-induced Tregs on bleomycin-induced dermal fibrosis and clarify the role of the Th17/Treg balance in SSc fibrosis.

Synthesis of Azocine-Fused Indoles via Gold(I)-Catalyzed Cyclization of Azido-alkynes.

Herein, we report a gold(I)-catalyzed cascade cyclization of azido-alkynes bearing an enol ester moiety, leading to indole-fused eight-membered rings. This method allows for the one-step construction of indole and tetrahydroazocin-4-one via an α-imino gold carbene intermediate. The resulting scaffold would be useful for accessing natural products with an eight-membered ring-fused indole moiety.

Receptor-independent regulation of Gα13 by alpha-1-antitrypsin C-terminal peptides.

Alpha-1-antitrypsin (AAT), a circulating serine protease inhibitor, is an acute inflammatory response protein with anti-inflammatory functions. The C-terminal peptides of AAT are found in various tissues and have been proposed as putative bioactive peptides with multiple functions, but its mechanism of action remains unclear. We previously reported that a mouse AAT C-terminal peptide of 35 amino acids (mAAT-C) penetrates plasma membrane and associates guanine nucleotide-binding protein subunit alpha 13 (Gα13).

Neonatal gut microbiota and risk of developing food sensitization and allergy.

Background: Food sensitization (FS) develops in early infancy and is a risk factor for subsequent food allergy (FA). Recent evidence suggests relationships of gut microbiota with FS and FA. However, little is known about the role of neonatal gut microbiota in the pathobiology of these manifestations.

Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles.

Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response to mild external heating. We constructed two types of polymeric micelles, DBCO-TRM and Az-TRM, having a thermo-responsive polymer shell based on N-isopropylacrylamide (NIPAAm) and incorporating alkyne and azide moieties, respectively.

Microplastics in sea ice drifted to the Shiretoko Peninsula, the southern end of the Sea of Okhotsk.

Sea ice is regarded as a temporal sink and carrier of microplastics (MPs). Nevertheless, knowledge and understanding of MPs in sea ice remain sparse. This study investigated the abundance, composition, size (> 30 μm), and shape of MPs in four sea-ice cores retrieved at the southern end of the Sea of Okhotsk.

Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity.

Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours. Salmonella enterica Typhimurium (STm) is well-studied amongst bacterial vectors due to advantages in genetic modification and metabolic adaptation. A longstanding paradox is the redundancy of T cells for treatment efficacy; instead, STm BCT depends on innate phagocytes for tumour control.

Protective effect of mesenchymal stromal cells in diabetic nephropathy: the In vitro and In vivo role of the M-Sec-tunneling nanotubes.

Mitochondrial dysfunction plays an important role in the development of podocyte injury in diabetic nephropathy (DN). Tunnelling nanotubes (TNTs) are long channels that connect cells and allow organelle exchange. Mesenchymal stromal cells (MSCs) can transfer mitochondria to other cells through the M-Sec-TNTs system.

A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.

Genetic studies in mice have shown that the zinc finger transcription factor BCL11B has an essential role in regulating early T cell development and neurogenesis. A de novo heterozygous missense BCL11B variant, BCL11B, was isolated from a patient with T cell deficiency and neurological disorders. Here, we show that mice harboring the corresponding Bcl11b mutation show the emergence of natural killer (NK)/group 1 innate lymphoid cell (ILC1)-like NKp46 cells in the thymus and reduction in TBR1 neurons in the neocortex, which are observed with loss of Bcl11a but not Bcl11b.

Circulatory characteristics of early mobilization after surgery for bilateral pheochromocytoma: a case report.

Background: Surgical treatment of pheochromocytomas is associated with circulatory dynamics instability, necessitating systemic management of the patient in the intensive care unit after surgery. Early mobilization after pheochromocytoma surgery is not described in the guidelines, and to our knowledge, no reports have specifically focused on circulatory dynamics during early mobilization after surgery.

Case Presentation: A 31-year-old Japanese woman was diagnosed with bilateral pheochromocytoma and underwent a second-stage adrenalectomy for bilateral pheochromocytoma at our hospital.

Comparative Study of Current-Induced Torque in Cr/CoFeB/MgO and W/CoFeB/MgO.

Orbital torque (OT) in magnetic heterostructures has been actively discussed in terms of its actual existence and usefulness in comparison to the spin-orbit torque (SOT) that shows promise for next-generation magnetoresistive random access memories. The objectives of this study are 2-fold: (i) making an apples-to-apples comparison in two representative stacks where OT and SOT are expected to dominate and (ii) examining the potential emergence of OT in archetypal SOT stacks. Cr/CoFeB/MgO and W/CoFeB/MgO are chosen as the OT- and SOT-dominant systems, respectively.

Development of Ribityllumazine Analogue as Mucosal-Associated Invariant T Cell Ligands.

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells abundant in human tissues that play a significant role in defense against bacterial and viral infections and in tissue repair. MAIT cells are activated by recognizing microbial-derived small-molecule ligands presented by the MHC class I related-1 protein. Although several MAIT cell modulators have been identified in the past decade, potent and chemically stable ligands remain limited.

RelB and C/EBPα critically regulate the development of Peyer's patch mononuclear phagocytes.

To establish protection against harmful foreign antigens, the small intestine harbors guardian sites called Peyer's patches (PPs). PPs take up antigens through microfold (M) cells and transfer them to the sub-epithelial dome (SED), which contains a high density of mononuclear phagocytes (MPs), for T cell-priming. Accumulating evidence indicates that SED-MPs have unique functions other than T cell-priming to facilitate mucosal immune responses; however, the crucial factors regulating the functions of SED-MPs have not been determined.

Food antigens suppress small intestinal tumorigenesis.

Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer's patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens.

Block Copolymer-Directed Single-Diamond Hybrid Structures Derived from X-ray Nanotomography.

Block copolymers are recognized as a valuable platform for creating nanostructured materials. Morphologies formed by block copolymer self-assembly can be transferred into a wide range of inorganic materials, enabling applications including energy storage and metamaterials. However, imaging of the underlying, often complex, nanostructures in large volumes has remained a challenge, limiting progress in materials development.

Comparative Analysis of Nutritional Advice and a Combined Approach for Addressing Impending Stunting in Infants: A Clinical Trial.

Weight faltering (WF) has been associated with stunting and with long-term adverse consequences for health and development. Nutritional care for managing WF may consist of giving nutritional advice (NA) and/or provision of oral nutrition supplements (ONSs). In this study, we aimed to evaluate practical management options in the community for infants with WF aged 6-12 months.

Relationship between radiation dose and markers of insulin resistance and inflammation in atomic bomb survivors.

Context: In recent studies of childhood cancer survivors, diabetes has been considered a late effect associated with high therapeutic doses of radiation therapy. Our recent study of atomic bomb (A-bomb) survivors also suggested an association between radiation dose and diabetes incidence, with exposure city and age at exposure as radiation dose effect modifiers. Insulin resistance mediated by systemic inflammation and abnormal body composition has been suggested as a possible primary mechanism for the incidence of diabetes after total body irradiation, however, no studies have examined low-to- moderate radiation exposure (<4 Gy) and insulin resistance in A-bomb survivors.

Compounds Designs of CK2α Inhibitors Derived from Virtual Screening Hit Compounds by Computational Chemistry with Crystallography.

Protein kinase CK2 type α (CK2α) inhibitors are expected to be a new anticancer drug and a treatment for nephritis. Virtual screening for CK2α inhibitors has been conducted and active compounds with various scaffolds have been obtained. Research on compound optimization is currently in progress for some of them with the aim of improving their activity.