Structure-Based Design of Novel TLR7/8 Agonist Payloads Enabling an Immunomodulatory Conjugate Approach.

Dual activation of the TLR7 and TLR8 pathways leads to the production of type I interferon and proinflammatory cytokines, resulting in efficient antigen presentation by dendritic cells to promote T-cell priming and antitumor immunity. We developed a novel series of TLR7/8 dual agonists with varying ratios of TLR7 and TLR8 activity for use as payloads for an antibody-drug conjugate approach. The agonist-induced production of several cytokines in human whole blood confirmed their functional activity.

Correction: The peak viscosity of decaying foam with natural drainage and coarsening.

Correction for 'The peak viscosity of decaying foam with natural drainage and coarsening' by Wei Yu and Jack H. Y. Lo, , 2024, , 4964-4971, https://doi.

Hematologic Complications of Pregnancy.

Hematologic complications are common in pregnancy and can significantly impact both maternal and fetal health. Recognizing and treating these complications can be challenging due to the limited evidence available to guide clinical consultants. Iron deficiency anemia is the most prevalent hematologic issue in pregnancy and often occurs due to increased maternal blood volume and the nutritional demands of the growing fetus.

Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut-liver axis.

Transmembrane-6 superfamily member 2 (TM6SF2) regulates hepatic fat metabolism and is associated with metabolic dysfunction-associated steatohepatitis (MASH). TM6SF2 genetic variants are associated with steatotic liver disease. The pathogenesis of MASH involves genetic factors and gut microbiota alteration, yet the role of host-microbe interactions in MASH development remains unclear.

Complement 3a receptor 1 on macrophages and Kupffer cells is not required for the pathogenesis of metabolic dysfunction-associated steatotic liver disease.

Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood.