Transfection Potency of Lipid Nanoparticles Containing mRNA Depends on Relative Loading Levels.

When formulating mRNA into lipid nanoparticles (LNP), various copy numbers of mRNA are encapsulated, leading to a distribution of mRNA loading levels within the LNPs. It is unclear whether the mRNA loading level affects the functional delivery of the message. Here we show that depending on the mRNA loading level, LNPs exhibit distinct mass densities and can be fractionated via ultracentrifugation.

A Comparison of Hypotension, Bradycardia, and Hypoxia Incidence between the Use of Remimazolam and Other Sedative Agents during Colonoscopy Procedures: A Systematic Review and Meta-Analysis.

Remimazolam is a newly developed sedative agent. The results of previous meta-analyses highlight the strengths of remimazolam for use during colonoscopy procedures. The primary aim of the present study was to investigate whether, in patients undergoing colonoscopy procedures (P), the use of remimazolam (I) compared with other sedative agents (C) could lead to a greater incidence of hypotension, bradycardia, and hypoxia (O).

Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity.

Self-amplifying RNA (saRNA) is a next-generation RNA platform derived from an alphavirus that enables replication in host cytosol, offering a promising shift from traditional messenger RNA (mRNA) therapies by enabling sustained protein production from minimal dosages. The approval of saRNA-based vaccines, such as the ARCT-154 for COVID-19 in Japan, underscores its potential for diverse therapeutic applications, including vaccine development, cancer immunotherapy, and gene therapy. This study investigates the role of delivery vehicle and administration route on saRNA expression kinetics and reactogenicity.

Discovery of Novel Lin28 Inhibitors to Suppress Cancer Cell Stemness.

Lin28 is a pluripotency factor that regulates cancer cell stem-like phenotypes to promote cancer development and therapy-resistant tumor progression. It acts through its cold shock domain and zinc knuckle domain (ZKD) to interact with the Let-7 pre-microRNA and block Let-7 biosynthesis. Chemical inhibition of Lin28 from interacting with Let-7 presents a therapeutic strategy for cancer therapy.

Incidental finding of severe hyperkalemia in a patient with end-stage renal disease during video-assisted lung lobectomy: A case report.

Patients with end-stage renal disease are at risk of developing hyperkalemia and acidosis, both of which have disastrous sequelae during elective video-assisted thoracic surgery for lung cancer. Herein, we present a case where severe hyperkalemia and combined acidosis were incidentally found in a 68-year-old man with the end-stage renal disease after establishing one-lung ventilation during video-assisted lobectomy. There was no significant instability of vital signs, abnormality of perioperative electrocardiography, or malignant arrhythmia.

A Comparison of McGrath Videolaryngoscope versus Macintosh Laryngoscope for Nasotracheal Intubation: A Systematic Review and Meta-Analysis.

Background: In this study, it was shown that the routine use of McGrath videolaryngoscopy may improve intubation success rates. The benefits to using a videolaryngoscope in nasotracheal intubation were also demonstrated. However, no solid evidence concerning the effectiveness of the use of McGrath videolaryngoscopes in nasotracheal intubation has previously been reported.

Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy.

Clinically used topoisomerase II (TOP2) inhibitors are poison inhibitors that induce DNA damage to cause cancer cell death. However, they can also destroy benign cells and thereby show serious side effects, including cardiotoxicity and drug-induced secondary malignancy. New TOP2 inhibitors with a different mechanism of action (MOA), such as catalytic TOP2 inhibitors, are needed to more effectively control tumor growth.

LIN28B promotes the development of neuroendocrine prostate cancer.

Therapy-induced neuroendocrine prostate cancer (t-NEPC) is a highly aggressive subtype of prostate cancer with poor patient survival. Emerging evidence indicates that t-NEPC can develop when prostate adenocarcinoma cells acquire cancer stem-like cell signaling in the presence of androgen receptor inhibition, followed by redifferentiation toward neuroendocrine lineage and subsequent t-NEPC progression. Whether the stem-like signaling is controlled by the core pluripotency stem cell genes (e.