Machine learning for antimicrobial peptide identification and design.

Artificial intelligence (AI) and machine learning (ML) models are being deployed in many domains of society and have recently reached the field of drug discovery. Given the increasing prevalence of antimicrobial resistance, as well as the challenges intrinsic to antibiotic development, there is an urgent need to accelerate the design of new antimicrobial therapies. Antimicrobial peptides (AMPs) are therapeutic agents for treating bacterial infections, but their translation into the clinic has been slow owing to toxicity, poor stability, limited cellular penetration and high cost, among other issues.

Active targeting of type 1 diabetes therapies to pancreatic beta cells using nanocarriers.

Type 1 diabetes is an autoimmune disease characterised by the destruction of pancreatic beta cells, resulting in lifelong insulin dependence. Although exogenous insulin can maintain glycaemic control, this approach does not protect residual or replacement pancreatic beta cells from immune-mediated death. Current therapeutics designed to protect functional beta cell mass or promote beta cell proliferation and regeneration can have off-target effects, resulting in higher dose requirements and adverse side effects.

Development of an G Protein-Coupled Receptor Fragment Molecule Screening Approach with High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance.

Small molecules are essential for investigating the pharmacology of membrane proteins and remain the most common approach for therapeutically targeting them. However, most experimental small molecule screening methods require ligands containing radiolabels or fluorescent labels and often involve isolating proteins from their cellular environment. Additionally, most conventional screening methods are suited for identifying compounds with moderate to higher affinities ( < 1 μM) and are less effective at detecting lower affinity compounds, such as weakly binding molecular fragments.

Local erythropoiesis directs oxygen availability in bone fracture repair.

Bone fracture ruptures blood vessels and disrupts the bone marrow, the site of new red blood cell production (erythropoiesis). Current dogma holds that bone fracture causes severe hypoxia at the fracture site, due to vascular rupture, and that this hypoxia must be overcome for regeneration. Here, we show that the early fracture site is not hypoxic, but instead exhibits high oxygen tension (> 55 mmHg, or 8%), similar to the red blood cell reservoir, the spleen.

Improved patient reported outcomes with knotless double-row rotator cuff repair with and without lateral row biceps tenodesis at 2- and 5-years.

Background: The purpose of this study is to report outcomes of an arthroscopic knotless double-row (DR) rotator cuff repair (RCR) technique at 2- and 5- years postoperatively, and to compare clinical outcomes in patients undergoing knotless DR RCR with incorporated lateral row biceps tenodesis (LRT) vs. those without LRT.

Methods: All primary RCR surgeries were performed by a single surgeon at a single institution using a knotless transosseous equivalent (TOE) technique.