The Overlooked Stereoisomers of the Ionizable Lipid ALC315.

Lipid nanoparticles (LNPs) are a powerful delivery platform for nucleic acid therapeutics such as mRNA vaccines and gene therapies. Central to their success are ionizable lipids, which facilitate the cellular uptake and endosomal escape of nucleic acids. However, achieving a high delivery efficiency often comes with the drawback of increased cytotoxicity.

A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity.

The global circulation of SARS-CoV-2 in human populations has driven the emergence of Omicron subvariants, which have become highly diversified through recombination. In late 2024, SARS-CoV-2 Omicron XEC variant emerged from the recombination of two JN.1 progeny, KS.

Distinct characteristics of brain metastasis in lung adenocarcinoma: development of high-confidence cell lines.

Lung cancer is a leading cause of cancer-related deaths worldwide, with brain metastasis occurring in approximately 30-55% of patients, particularly in lung adenocarcinoma. Due to the challenges in obtaining genuine brain metastasis tumor cells, researchers commonly use nude mouse models to establish brain metastasis cell lines, though traditional methods have limitations such as high costs, lengthy timeframes, and the need for specialized imaging equipment. To address these issues, we developed an improved approach by performing low cell number circulating intracranial injections (500-4000 cells) in nude mice, successfully establishing the H1975-BM1, BM2, and BM3 cell lines.

Mechanochemistry-Induced Universal Hydrogel Surface Modification for Orientation and Enhanced Differentiation of Skeletal Muscle Myoblasts.

Micropatterned surface substrates containing topographic cues offer the possibility of programming tissue organization as a cell template by guiding cell alignment, adhesion, and function. In this study, we developed and used a force stamp method to grow aligned micropatterns with tunable chemical properties and elasticity on the surface of hydrogels based on a force-triggered polymerization mechanism of double-network hydrogels to elucidate the underlying mechanisms by which cells sense and respond to their mechanical and chemical microenvironments. In this work, we describe the impact of aligned micropatterns on the combined effects of microstructural chemistry and mechanics on the selective adhesion, directed migration, and differentiation of myoblasts.

Hydrogel PCDME creates pancreatic cancer stem cells in OXPHOS metabolic state with TXNIP elevation.

Pancreatic cancer is known as one of the poor prognostic cancers, and the most of patients are unable to undergo radical resection due to local progression or distant metastasis at initial diagnosis. In spite of the advancements in surgery and chemotherapy, there are many cases of recurrence after surgery or chemoradiotherapy mainly due to the presence of cancer stem cells (CSCs). CSCs are potential therapeutic target, but current issue is that an identification of CSCs is difficult since they are only present in a small number of tumor cells.

SLC13A5 plays an essential role in the energy shift to oxidative phosphorylation in cisplatin-resistant mesothelioma stem cells.

Mesothelioma is a highly aggressive tumor affecting an increasing number of patients worldwide. Owing to the poor clinical outcomes associated with current therapies, the development of novel therapies that target cancer stem cells (CSCs) is desirable. Here, we examined the applicability of our previously established hydrogel-based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) -like cells.

Establishment of a novel method for differentiating into dopaminergic neurons using charged hydrogels.

Parkinson's disease (PD) is a neurodegenerative disease primarily affecting the central nervous system and impacting both the motor system and non-motor systems. Although administration of L-DOPA is effective, it is not a fundamental treatment and has side effects such as diurnal fluctuation and dyskinesia, highlighting the need for new treatment methods. There is a growing interest in dopaminergic neuron transplantation as a potential treatment.

Analysis of synthetic polymer hydrogel-based generation of leukemia stem cells.

Leukemia stem cells (LSCs), capable of simultaneous self-renewal and differentiation, are resistant to chemotherapy and the cause of relapse in refractory cases of leukemia. As a method to rapidly generate LSCs has not been established, research on LSCs as therapeutic targets has been hampered. Here, we demonstrate that K562 leukemia cells acquired LSC properties with increase in stemness markers such as CD34, Oct3/4, and Nanog and metabolic alterations towards OXPHOS by culturing cells on synthetic polymer hydrogels.

Transformed gastric mucosa-associated lymphoid tissue lymphoma originating in the colon and developing metachronously after eradication: A case report.

Background: () eradication treatment for primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma has already been established. However, t (11;18) (q21;q21)/ translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to achieve. In addition, trisomy 18 may be associated with diffuse large B-cell lymphoma (DLBCL) transformation of gastric MALT lymphoma.

[Histiocytic sarcoma derived from the same origin as splenic marginal zone lymphoma revealed by exome analysis].

Histiocytic sarcoma (HS) is a rare aggressive hematological malignancy reported to occur secondary to B cell lymphoma. We report a case of HS secondary to splenic marginal zone lymphoma (SMZL) complicated by autoimmune hemolytic anemia (AIHA) in a 64-year-old man. He was referred to our department with anemia and was diagnosed as having AIHA.

Caging Bioactive Triarylimidazoles: An Approach to Create Visible Light-Activatable Drugs.

Imidazoles are crucial structural components in a variety of small-molecule inhibitors designed to target different kinases in anticancer treatment. However, the effectiveness of such inhibitors is often hampered by nonspecific effects and the development of resistance. Photopharmacology provides a compelling solution by enabling external control over drug activity with spatiotemporal precision.

Clinical outcome, radiological findings, and genetic features of IDH-mutant brainstem glioma in adults.

Background: With the recent advent of genetic testing, IDH-mutant glioma has been found among adult brainstem gliomas. However, the clinical outcome and prognosis of IDH-mutant brainstem gliomas in adults have not been elucidated. This study aimed to investigate the clinical outcome, radiological findings, and genetic features of adult patients with IDH-mutant diffuse brainstem gliomas.

Involvement of SARS-CoV-2 accessory proteins in immunopathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the largest single-stranded RNA virus known to date. Its genome contains multiple accessory protein genes that act against host immune responses but are not required for progeny virus production. The functions of the accessory proteins in the viral life cycle have been examined, but their involvement in viral pathogenicity remains unclear.

Akaluc bioluminescence offers superior sensitivity to track dynamics of SARS-CoV-2 infection.

Monitoring viral dynamics can improve our understanding of pathogenicity and tissue tropism. Because the gene size of RNA viruses is typically small, NanoLuc is the primary choice for accommodation within viral genome. However, NanoLuc/Furimazine and also the conventional firefly luciferase/D-luciferin are known to exhibit relatively low tissue permeability and thus less sensitivity for visualization of deep tissue including lungs.

Structure-changeable luminescent Eu(III) complex as a human cancer grade probing system for brain tumor diagnosis.

Accurate determination of human tumor malignancy is important for choosing efficient and safe therapies. Bioimaging technologies based on luminescent molecules are widely used to localize and distinguish active tumor cells. Here, we report a human cancer grade probing system (GPS) using a water-soluble and structure-changeable Eu(III) complex for the continuous detection of early human brain tumors of different malignancy grades.

A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging.