Design of ()-3-(5-Thienyl)carboxamido-2-aminopropanoic Acid Derivatives as Novel NMDA Receptor Glycine Site Agonists: Variation in Molecular Geometry to Improve Potency and Augment GluN2 Subunit-Specific Activity.

NMDA receptor ligands have therapeutic potential in neurological and psychiatric disorders. We designed ()-3-(5-thienyl)carboxamido-2-aminopropanoic acid derivatives with nanomolar agonist potencies at NMDA receptor subtypes (GluN12/A-D). These compounds are superagonists at GluN1/2C compared to glycine and partial to full agonists at GluN1/2A and GluN1/2D but display functional antagonism at GluN1/2B due to low agonist efficacy.

MARVELD1 Promotes the Invasiveness in Pancreatic Adenocarcinoma through the Activation of Epithelial-to-Mesenchymal Transition.

Background: MARVEL domain-containing 1 (MARVELD1) has been implicated in the progression of several cancers, but its role in pancreatic adenocarcinoma (PAAD) remains poorly understood.

Methods: RNA-seq data from the TCGA-PAAD and GTEx-Pancreas cohorts were analyzed to assess MARVELD1 expression. Stable MARVELD1 knockdown and overexpression were conducted in BxPC3 and PANC-1 cells.

Application of adoptive cell therapy in malignant melanoma.

Cutaneous melanoma is one of the most aggressive skin cancers originating from skin pigment cells. Patients with advanced melanoma suffer a poor prognosis and generally cannot benefit well from surgical resection and chemo/target therapy due to metastasis and drug resistance. Thus, adoptive cell therapy (ACT), employing immune cells with specific tumor-recognizing receptors, has emerged as a promising therapeutic approach to display on-tumor toxicity.

Prevalence and risk factors of the most common multimorbidity among Canadian adults.

Background: The number of persons living with multimorbidity-defined as the co-occurrence of at least two chronic conditions in the same individual-is growing globally, especially in developed countries. Traditionally, this increase has been attributed to a growing aging population, sedentary lifestyle, obesity, low socioeconomic status, and individual genetic susceptibility.

Objective: To investigate the prevalence and associated risk factors of the most common multimorbidity (MCM) among Canadian middle-aged and older adults.

A double dissociation between semantic and spatial cognition in visual to default network pathways.

Processing pathways between sensory and default mode network (DMN) regions support recognition, navigation, and memory but their organisation is not well understood. We show that functional subdivisions of visual cortex and DMN sit at opposing ends of parallel streams of information processing that support visually mediated semantic and spatial cognition, providing convergent evidence from univariate and multivariate task responses, intrinsic functional and structural connectivity. Participants learned virtual environments consisting of buildings populated with objects, drawn from either a single semantic category or multiple categories.