The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms.

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to depressive disorders. This review elucidates the complex interplay between peripheral and central immune components underlying depressive disorder pathology.

IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility.

IgA antibodies are critical components of the mucosal immune barrier, providing essential first-line defense against viral infections. In this study, we investigated the impact of antibody class switching on neutralization efficacy by engineering recombinant antibodies of different isotypes (IgA1, IgG1) with identical variable regions from SARS-CoV-2 convalescent patients. A potent, broad-spectrum neutralizing monoclonal antibody CAV-C65 exhibited a ten-fold increase in neutralization potency upon switching from IgG1 to IgA1 monomer.

Macrocyclic peptides as a new class of targeted protein degraders.

Targeted protein degraders, in the form of proteolysis targeting chimaeras (PROTACs) and molecular glues, leverage the ubiquitin-proteasome system to catalytically degrade specific target proteins of interest. Because such molecules can be extremely potent, they have attracted considerable attention as a therapeutic modality in recent years. However, while targeted degraders have great potential, they are likely to face many of the same challenges as more traditional small molecules when it comes to their development as therapeutics.

Development, validation, and usage of metrics to evaluate the quality of clinical research hypotheses.

Objectives: Metrics and instruments can provide guidance for clinical researchers to assess their potential research projects at an early stage before significant investment. Furthermore, metrics can also provide structured criteria for peer reviewers to assess others' clinical research manuscripts or grant proposals. This study aimed to develop, test, validate, and use evaluation metrics and instruments to accurately, consistently, systematically, and conveniently assess the quality of scientific hypotheses for clinical research projects.