Dominant effect of a single amino acid mutation in the motor domain of myosin VI on hearing in mice.

An unconventional myosin, myosin VI gene (MYO6), contributes to recessive and dominant hearing loss in humans and mice. The Kumamoto shaker/waltzer (ksv) mouse is a model of deafness resulting from a splice-site mutation in Myo6. While ksv/ksv homozygous mice are deaf due to cochlear hair cell stereocilia fusion at the neonatal stage, the hearing phenotypes of ksv/+ heterozygous mice have been less clear.

Analysis of Powder Properties of Pharmaceutical Excipients Using a Constant-Volume Shear Tester.

Powders used in pharmaceuticals require good flowability. The angle of repose and compressibility index are often used to measure the flowability of pharmaceutical powders. However, confirming the relationship between external forces and flowability for smooth powder handling is necessary.

γ-Secretase Cleaves Bifunctional Fatty Acid-Conjugated Small Molecules with Amide Bonds in Mammalian Cells.

Connecting two small molecules, such as ligands, fluorophores, or lipids, together via a linker with amide bonds is a widely used strategy to generate synthetic bifunctional molecules for various biological and biomedical applications. Such bifunctional molecules have been used in live-cell experiments under the assumption that they should be stable in cells. However, we recently found that a membrane-targeting bifunctional molecule, composed of a lipopeptide and the small-molecule ligand trimethoprim, referred to as mgcTMP, underwent amide-bond cleavage in mammalian cells.

Comparison of Adverse Event Profiles of Amphotericin B Formulations Using Real-World Data.

Amphotericin B deoxycholate (AMPH-B) is a polyene macrolide with antifungal activity. Liposomal AMPH-B (L-AMB) was developed to reduce side effects while maintaining antifungal activity. This study was aimed at evaluating and comparing the adverse event profiles of AMPH-B and L-AMB using a spontaneous reporting system.

Influence of Placenta Extract Intake on Periodontal Diseases and Oral Environment: A Case Series.

Background: The placenta extract is used as a dietary supplement. We aimed to investigate the effects of placenta extract on periodontal disease.

Case Presentation: In this study, placenta extract supplements were found to improve the oral environment of young and middle-aged Japanese women undergoing maintenance; after three months of taking placenta extract, bleeding upon probing was reduced.

Synthetic, Electrochemical, DFT, and Synchrotron X-ray Charge-Density Studies on Oxo-centered Triruthenium Clusters Supported by Electron-Withdrawing Carboxylates.

We herein report the synthesis, characterizations, and synchrotron X-ray charge-density studies of oxo-centered triruthenium(II,III,III) clusters [RuO(CHClCOO)(py)] () and [RuO(CHClCOO)(CO)(py)] () (py = pyridine). Dichloroacetate was chosen for its large scattering factor of the Cl atom, and its electron-withdrawing nature results in significant stabilization of the targeted lower-valent Ru state in the cluster framework. Multipole analysis revealed that the difference in electron populations between two crystallographically independent Ru centers is small for (Δ = 0.

Stable and inhalable powder formulation of mRNA-LNPs using pH-modified spray-freeze drying.

A powder formulation for mucosal administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is expected to be useful for respiratory diseases. Although freeze-drying is widely used to obtain solid formulations of mRNA-LNPs, highly hydrosoluble cryoprotectants, such as sucrose are necessary. However, sucrose is not a suitable excipient for inhalation powders because of its hygroscopic and deliquescence properties.

Molecular islands at the liquid-solid interface.

Molecular islands of various shapes and sizes composed of a few tens of molecules only are formed at the liquid-solid interface, at room temperature, by an alkoxylated dehydrobenzo[12]annulene (DBA) derivative. Molecules are packed into hexagons. Scanning tunneling microscopy reveals the variety in molecular island structures and their stability.

Supplementation of equine placenta extract on corneal wound in two dogs: Case report.

Background: Canine corneal disease is a common condition encountered in daily practice. If the depth of corneal damage is limited to the epithelial layer, healing is often straightforward; however, if it extends into the epithelial basement membrane or corneal parenchyma, surgical treatment is the treatment of choice. Moreover, in cases where there is an underlying disease or where the owner refuses surgical treatment, treatment options are often limited to eye drop treatment, which may be inadequate.

Development of Polyvinyl Alcohol (PVA) Nanofibers Containing Cationic Lipid/siRNA Complexes via Electrospinning: The Impact of PVA Characterization.

This study aimed to develop polyvinyl alcohol (PVA) nanofibers encapsulating 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/siRNA complexes via electrospinning for the delivery of nucleic acid-based drugs. It also focused on the influence of the intrinsic properties of PVA on the efficacy of the system. PVA nanofibers, with diameters of 300-400 nm, were obtained, within which the siRNA remained intact and the DOTAP/siRNA complexes were uniformly dispersed.

Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium.

Unlabelled: Endothelial Notch signaling is critical for tumor angiogenesis. Notch1 blockade can interfere with tumor vessel function but causes tissue hypoxia and gastrointestinal toxicity. Notch4 is primarily expressed in endothelial cells, where it may promote angiogenesis; however, effective therapeutic targeting of Notch4 has not been successful.

Chiral Solvent-Induced Homochiral Hierarchical Molecular Assemblies at the Liquid/Solid Interface.

We herein investigate the formation of homochiral hierarchical self-assembled molecular networks (SAMNs) via chirality induction by the coadsorption of a chiral solvent at the liquid/graphite interface by means of scanning tunneling microscopy (STM). In a mixture of achiral solvents, 1-hexanoic acid, and 1,2,4-trichlorobenzene, an achiral dehydrobenzo[12]annulene (DBA) derivative with three alkoxy and three hydroxy groups in an alternating manner forms chiral hierarchical triangular cluster structures through dynamic self-sorting. Enantiomorphous domains appear in equal probability.

Adsorption of Prochiral Solvent Molecules by Surface-Confined Chiral Supramolecular Assemblies: How Solvent Impacts on-Surface Chirality.

The understanding of supramolecular chirality in self-assembled molecular networks (SAMNs) on surfaces generates a lot of interest because of its relation to the production of chiral sensors, reactors, and catalysts. We herein report the adsorption of a prochiral solvent molecule in porous SAMNs formed by a chiral dehydrobenzo[12]annulene (cDBA) derivative. Through the prochirality recognition of a solvent molecule, the supramolecular chirality of the SAMN is switched: the cDBA exclusively forms a counter-clockwise pore through co-adsorption of the solvent molecule in prochiral 1,2,4-trichlorobenzene, while in 1-phenyloctane it produces the opposite chiral, clockwise pore.

Cryomilled electrospun nanofiber mats containing d-mannitol exhibit suitable for aerosol delivery of proteins.

Dry powder inhalers (DPIs) are the first choice for inhalation drug development. However, some conventional DPI formulation processes require heating, which may damage high molecular weight drugs such as proteins and nucleic acids. In this study, we propose a novel DPI preparation process that avoids the use of heat.

Unique presentation of acute neuro-Behçet's disease involving a cytotoxic edema core surrounded by vasogenic edema.

A 53-year-old woman with recurrent stomatitis, genital ulcers, and folliculitis was admitted to our hospital after experiencing visual disturbances for the past two weeks, and a non-throbbing headache for the past three days. She had also developed numbness in her left extremities. An ophthalmological examination revealed inflammatory changes in the eye.

Synthesis and Reactivity of an X-Shaped Molecule: Reversible Formation and Cleavage of a Four-Membered Ring in Response to External Stimuli.

We herein report the synthesis and reactivity of an X-shaped molecule featuring three four-membered rings (4MRs) arranged in a ladder configuration. This molecule exhibits a reversible opening and closure of the central 4MR upon exposure to light irradiation and thermal treatment. The central 4MR of this molecule is also cleaved via electrochemical and chemical reductions.

Macrocystic and non-necrotic salivary duct carcinoma of the submandibular gland: A case report.

Salivary duct carcinoma (SDC) is a major malignant salivary gland tumor that usually forms a solid tumor. Non-necrotic macrocystic SDCs have rarely been reported among salivary gland tumors. A 78-year-old Japanese man with a submandibular gland tumor was evaluated radiologically, pathologically, and immunohistochemically.

Heptagonal Molecular Tiling via Self-Assembly of Heptagonal Phenylene-Ethynylene Macrocycle at the Liquid-Solid Interface.

The molecular-level scrutinization of on-surface tiling garners considerable interest among scientists. Herein, we demonstrate molecular-level heptagonal tiling using the self-assembly of a heptagonal meta-phenylene-ethynylene macrocycle featuring 14 long alkoxy substituents at the liquid-graphite interface using scanning tunneling microscopy. This heptagonal macrocycle produces an antiparallel pattern at the 1-phenyloctane-graphite interface through van der Waals interactions between the alkoxy chains.

Controlled Release of Lysozyme Using Polyvinyl Alcohol-Based Polymeric Nanofibers Generated by Electrospinning.

Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics.

[Hemorrhagic Colon Cancer with Left Atrial Thrombus Formation after Anticoagulant Therapy Discontinuation-A Case Report].

The patient was a 72-year-old female. She had been taking rivaroxaban for chronic atrial fibrillation; however, she stopped taking it due to anemia and was hospitalized urgently. A contrast-enhanced computed tomography(CT)scan showed a 30 mm mass in the ascending colon, and a colonoscopy revealed ascending colon cancer(cT3, cN0, cM0, cStage Ⅱa).

Kikuchi-Fujimoto Disease in Human Leukocyte Antigen Partially Matched Siblings: A Case Study of Familial Susceptibility.

Kikuchi-Fujimoto disease (KFD) is a rare and self-limiting disorder that predominantly affects young individuals of Asian descent. This case report describes familial KFD in partially human leukocyte antigen (HLA)-matched siblings. An adolescent male presented with cervical lymphadenopathy and elevated lactate dehydrogenase (LDH) levels, diagnosed by biopsy as KFD; approximately one year later, his sister presented with similar symptoms.

CD40 is expressed in the subsets of endothelial cells undergoing partial endothelial-mesenchymal transition in tumor microenvironment.

Tumor progression and metastasis are regulated by endothelial cells undergoing endothelial-mesenchymal transition (EndoMT), a cellular differentiation process in which endothelial cells lose their properties and differentiate into mesenchymal cells. The cells undergoing EndoMT differentiate through a spectrum of intermediate phases, suggesting that some cells remain in a partial EndoMT state and exhibit an endothelial/mesenchymal phenotype. However, detailed analysis of partial EndoMT has been hampered by the lack of specific markers.

Homochiral hierarchical molecular assemblies through dynamic combination of conformational states of a single chiral building block at the liquid/solid interface.

We herein report the construction of homochiral, hierarchical self-assembled molecular networks (SAMNs) at the liquid/graphite interface using a single molecular building block, a chiral dehydrobenzo[12]annulene (cDBA) derivative with three chiral alkoxy and three hydroxy groups positioned in an alternating manner on the DBA core. The cDBA molecules form homochiral hierarchical SAMNs consisting of triangular clusters of several sizes, the size of which can be tuned by solvent polarity and solute concentration, reaching periodicities as large as 9.3 nm.