Feed efficiency (FE) is an important trait in the broiler industry due to its direct correlation to efficient muscle growth instead of fat deposition. The present study characterized and compared gene expression profiles in abdominal fat from broiler chickens of different FE levels to enhance the understanding of FE biology. Specifically, traditional whole-transcript RNA-sequencing (RNA-seq) and 3 UTR-sequencing (3 UTR-seq) were applied to 22 and 61 samples, respectively. Overall, these two sequencing techniques shared a high correlation (0.76) between normalized counts, although 3 UTR-seq showed a higher variance in sequencing and mapping performance statistics across samples and a lower rate of uniquely mapped reads. A higher percentage of 3 UTR-seq reads mapped to introns suggested the frequent presence of cleavage sites in introns, thus warranting future research to study its regulatory function. Differential expression analysis identified 1198 differentially expressed genes (DEGs) between high FE (HFE) and intermediate FE (IFE) chickens with False Discovery Rate < 0.05 and fold change > 1.2. The processes that were significantly enriched by the DEGs included extracellular matrix remodeling and mechanisms impacting gene expression at the transcriptional and translational levels. Gene ontology enrichment analysis suggested that the divergence in fat deposition and FE in broiler chickens could be associated with peroxisome and lipid metabolism possibly regulated by G0/G1 switch gene 2 (G0S2).

Ocular inflammation is commonly associated with eye disease or injury. Effective and sustained ocular delivery of therapeutics remains a challenge due to the eye physiology and structural barriers. Herein, we engineered a photocrosslinkable adhesive patch (GelPatch) incorporated with micelles (MCs) loaded with Loteprednol etabonate (LE) for delivery and sustained release of drug. The engineered drug loaded adhesive hydrogel, with controlled physical properties, provided a matrix with high adhesion to the ocular surfaces. The incorporation of MCs within the GelPatch enabled solubilization of LE and its sustained release within 15 days. In vitro studies showed that MC loaded GelPatch supported cell viability and growth. In addition, subcutaneous implantation of the MC loaded GelPatch in rats confirmed its in vivo biocompatibility and stability within 28 days. This non-invasive, adhesive, and biocompatible drug eluting patch can be used as a matrix for the delivery and sustained release of hydrophobic drugs.

The class III phosphoinositide 3-kinase (PI3K) Vps34 (also known as PIK3C3 in mammals) produces phosphatidylinositol 3-phosphate [PI(3)P] on both early and late endosome membranes to control membrane dynamics. We used Vps34-deficient cells to delineate whether Vps34 has additional roles in endocytic trafficking. In Vps34^-/- mouse embryonic fibroblasts (MEFs), transferrin recycling and EEA1 membrane localization were unaffected despite elevated Rab5-GTP levels. Strikingly, a large increase in Rab7-GTP levels, an accumulation of enlarged late endosomes, and decreased EGFR degradation were observed in Vps34-deficient cells. The hyperactivation of Rab7 in Vps34-deficient cells stemmed from the failure to recruit the Rab7 GTPase-activating protein (GAP) Armus (also known as TBC1D2), which binds to PI(3)P, to late endosomes. Protein-lipid overlay and liposome-binding assays reveal that the putative pleckstrin homology (PH) domain in Armus can directly bind to PI(3)P. Elevated Rab7-GTP led to the failure of intraluminal vesicle (ILV) formation and lysosomal maturation. Rab7 silencing and Armus overexpression alleviated the vacuolization seen in Vps34-deficient cells. Taken together, these results demonstrate that Vps34 has a previously unknown role in regulating Rab7 activity and late endosomal trafficking.