A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response.

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights.

Spatial and temporal dynamics of HDACs class IIa following mild traumatic brain injury in adult rats.

The fundamental role of epigenetic regulatory mechanisms involved in neuroplasticity and adaptive responses to traumatic brain injury (TBI) is gaining increased recognition. TBI-induced neurodegeneration is associated with several changes in the expression-activity of various epigenetic regulatory enzymes, including histone deacetylases (HDACs). In this study, PET/CT with 6-([F]trifluoroacetamido)-1- hexanoicanilide ([F]TFAHA) to image spatial and temporal dynamics of HDACs class IIa expression-activity in brains of adult rats subjected to a weight drop model of diffuse, non-penetrating, mild traumatic brain injury (mTBI).

Early prediction of clinical response to checkpoint inhibitor therapy in human solid tumors through mathematical modeling.

Background: Checkpoint inhibitor therapy of cancer has led to markedly improved survival of a subset of patients in multiple solid malignant tumor types, yet the factors driving these clinical responses or lack thereof are not known. We have developed a mechanistic mathematical model for better understanding these factors and their relations in order to predict treatment outcome and optimize personal treatment strategies.

Methods: Here, we present a translational mathematical model dependent on three key parameters for describing efficacy of checkpoint inhibitors in human cancer: tumor growth rate (), tumor-immune infiltration (), and immunotherapy-mediated amplification of anti-tumor response ().

Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.

There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state.

Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.

Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans.