Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation.

Conjugation chemistries are a major enabling technology for the development of drug delivery systems, from antibody-drug conjugates to antibody-targeted lipid nanoparticles inspired by the success of the COVID-19 vaccine. However, here it is shown that for antibody-targeted nanoparticles, the most popular conjugation chemistries directly participate in the activation of the complement cascade of plasma proteins. Their activation of complement leads to large changes in the biodistribution of nanoparticles (up to 140-fold increased uptake into phagocytes of the lungs) and multiple toxicities, including a 50% drop in platelet count.

Design, justification, and prototyping of the visible and infrared wide angle viewing system diagnostic for ITER equatorial port 12.

The ITER equatorial visible and infrared Wide Angle Viewing System (WAVS) will play a major role in the protection of plasma facing components by providing surface temperature measurements of these components. It will also image the plasma emission in the visible range. The WAVS is composed of 15 lines of sight located in four Equatorial Ports (EPs) 3, 9, 12, and 17.

Cardiac Specific Troponin I as Prognostic Factor among Non-COVID-19 Mechanically Ventilated Patients in a Tertiary Government Hospital: A Prospective Study.

Objective: The study aimed to investigate the relationship between cardiac Troponin I (cTnI) level and prognosis among mechanically ventilated patients in terms of mortality, prolonged mechanical ventilation, and tracheostomy rate.

Methods: This is a prospective cohort study conducted at Quirino Memorial Medical Center, a tertiary government hospital, over a period of ten (10) months. Seventy-six (76) mechanically ventilated adult patients admitted at the medical intensive care unit, surgical intensive care unit, medical wards, and centers for neurologic sciences were included in the study.

A percolation-type criticality threshold controls immune protein coating of surfaces.

When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, "deciding" whether to attack? We focus on the "complement" system of ∼40 blood proteins that bind microbes, nanoparticles, and medical devices, initiating inflammation. We show a sharp threshold for complement activation upon varying a fundamental material parameter, the surface density of potential complement attachment points.

Insights into Metabolic Reprogramming in Tumor Evolution and Therapy.

Cancer remains a global health challenge, characterized not just by uncontrolled cell proliferation but also by the complex metabolic reprogramming that underlies its development and progression. This review delves into the intricate relationship between cancer and its metabolic alterations, drawing an innovative comparison with the cosmological concepts of dark matter and dark energy to highlight the pivotal yet often overlooked role of metabolic reprogramming in tumor evolution. It scrutinizes the Warburg effect and other metabolic adaptations, such as shifts in lipid synthesis, amino acid turnover, and mitochondrial function, driven by mutations in key regulatory genes.