Lineage-Specific Class-A GPCR Dynamics Reflect Diverse Chemosensory Adaptations in Lophotrochozoa.

Sensing external chemosensory cues via Class-A G protein-coupled receptors (GPCRs) is crucial for a multitude of behavioral and biological functions, influencing animal evolution and ecological adaptations. While extensively studied in vertebrates and echinoderms, the role of GPCR-mediated chemoreception in major protostome clades like Lophotrochozoa remains obscure despite their remarkable ecological adaptations across diverse aquatic and terrestrial environments. Utilizing 238 lophotrochozoan genomes across eight phyla, we conducted a large-scale comparative genomics analysis to identify lineage-specific expansions of Class-A GPCR subsets that are likely adapted for chemoreception.

TRIM32 regulates insulin sensitivity by controlling insulin receptor degradation in the liver.

Impaired insulin receptor signaling is strongly linked to obesity-related metabolic conditions like non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes (T2DM). However, the exact mechanisms behind impaired insulin receptor (INSR) signaling in obesity induced by a high-fat diet remain elusive. In this study, we identify an E3 ubiquitin ligase, tripartite motif-containing protein 32 (TRIM32), as a key regulator of hepatic insulin signaling that targets the insulin receptor (INSR) for ubiquitination and proteasomal degradation in high-fat diet (HFD) mice.

Antisense Oligonucleotide Embedded Context Responsive Nanoparticles Derived from Synthetic Ionizable Lipids for lncRNA Targeted Therapy of Breast Cancer.

The long noncoding RNAs (lncRNA) are primarily associated with several essential gene regulations but are also connected to cancer metabolism and progression. HOTAIR and MALAT1 are two such lncRNAs that are detected in malignancies of various origins and are responsible for the poor prognosis of cancer patients. Due to these factors, the lncRNAs have emerged as prime targets for the development of anticancer therapeutics.

Emerging Roles of Gossypol in Therapy: Innovations in Prodrug Design and Nanoformulation Frontiers.

Stimuli activatable systems have the potential to deliver drugs to targeted areas by releasing therapeutic agents in response to diseased specific microenvironments such as the acidic environment commonly found in diseased tissues. This review article focuses on gossypol, a bioactive compound with inherent toxicity attributed to various factors, including the presence of its formyl groups. It highlights the potential of imine-linked gossypol-based prodrugs and nanoparticle formulations for targeted delivery and controlled release.

Synthetically Tunable Suprahybrid Nanoparticle Platform for the Efficacious Delivery of Therapeutics.

The discovery of lipid-hybrid nanosystems has offered potential solutions to various drug delivery and theranostic challenges. However, in many instances, the commonly used lipids and other components in these systems often pose challenges related to their solubility, physicochemical properties, immune compatibility, and limited synthetic tunability. In this work, we introduce a synthetically tunable supramolecular scaffold with amphiphilic characteristics based on the calix[4]arene macrocyclic system.