Phenotypic screens for SIRPA expression reveal RAB21 as a general regulator of macrophage surface identity.

Factors influencing the macrophage surfaceome define macrophage identity and behavior. Here, we use genome-wide phenotypic screens to identify genes affecting the accessibility and surface expression of macrophage signal regulatory protein alpha (SIRPA). Our data are consistent with previous evidence but also implicate glutaminyl-peptide cyclotransferase-like (QPCTL) in cis CD47-SIRPA interactions.

Discovering nanoparticle corona ligands for liver macrophage capture.

Liver macrophages capture circulating nanoparticles and reduce their delivery to target organs. Serum proteins adsorb to the nanoparticle surface after administration. However, the adsorbed serum proteins and their cognate cell receptors for removing nanoparticles from the bloodstream have not been linked.

Cellular Glycocalyx Affects Nanoparticle Access to Cell Membranes and Uptake.

Understanding nanoparticle interactions with cells is fundamental to designing them for medical applications. Nanoparticles must interface with the cell surface to be bound and taken up. The glycocalyx is a carbohydrate layer coating the cell surface, rendering it negatively charged.

The pathways for nanoparticle transport across tumour endothelium.

The active transport and retention principle is an alternative mechanism to the enhanced permeability and retention effect for explaining nanoparticle tumour delivery. It postulates that nanoparticles actively transport across tumour endothelial cells instead of passively moving through gaps between these cells. How nanoparticles transport across tumour endothelial cells remains unknown.

Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing.

Effective genome editing requires a sufficient dose of CRISPR-Cas9 ribonucleoproteins (RNPs) to enter the target cell while minimizing immune responses, off-target editing, and cytotoxicity. Clinical use of Cas9 RNPs currently entails electroporation into cells ex vivo, but no systematic comparison of this method to packaged RNP delivery has been made. Here we compared two delivery strategies, electroporation and enveloped delivery vehicles (EDVs), to investigate the Cas9 dosage requirements for genome editing.

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing.

Effective genome editing requires a sufficient dose of CRISPR-Cas9 ribonucleoproteins (RNPs) to enter the target cell while minimizing immune responses, off-target editing and cytotoxicity. Clinical use of Cas9 RNPs currently entails electroporation into cells , but no systematic comparison of this method to packaged RNP delivery has been made. Here we compared two delivery strategies, electroporation and enveloped delivery vehicles (EDVs), to investigate the Cas9 dosage requirements for genome editing.

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat or even cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped Delivery Vehicles (EDVs) are engineered virally-derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication components in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

Tibial Plateau Fracture With Use of Tibia Strut and Bone Filler in a 37-Year-Old Male: A Case Report.

Tibial plateau fractures (TPFs) are orthopedic challenges with multiple injury modalities and clinical presentations. TPFs are often classified using the Schatzker classification system, which can dictate management. In our case, a 37-year-old male presented at an orthopedic specialty hospital with right knee pain after a fall from a truck ramp.

The exit of nanoparticles from solid tumours.

Nanoparticles enter tumours through endothelial cells, gaps or other mechanisms, but how they exit is unclear. The current paradigm states that collapsed tumour lymphatic vessels impair the exit of nanoparticles and lead to enhanced retention. Here we show that nanoparticles exit the tumour through the lymphatic vessels within or surrounding the tumour.

Toward Predicting Nanoparticle Distribution in Heterogeneous Tumor Tissues.

Nanobio interaction studies have generated a significant amount of data. An important next step is to organize the data and design computational techniques to analyze the nanobio interactions. Here we developed a computational technique to correlate the nanoparticle spatial distribution within heterogeneous solid tumors.

Indications of musculoskeletal health in deceased male individuals with lower-limb amputations: comparison to non-amputee and diabetic controls.

Individuals with lower-limb amputations, many of whom have type 2 diabetes, experience impaired musculoskeletal health. This study: (1) compared residual and intact limbs of diabetic and non-diabetic post-mortem individuals with amputation to identify structures vulnerable to injury, and (2) compared findings to diabetic and healthy control groups to differentiate influences of amputation and diabetes on musculoskeletal health. Postmortem CT scans of three groups, ten individuals each, were included: (1) individuals with transtibial or transfemoral amputations, half with diabetes (2) diabetic controls, and (3) healthy controls.

Nanoparticles Bind to Endothelial Cells in Injured Blood Vessels via a Transient Protein Corona.

Nanoparticles travel through blood vessels to reach disease sites, but the local environment they encounter may affect their surface chemistry and cellular interactions. Here, we found that as nanoparticles transit through injured blood vessels they may interact with a highly localized concentration of platelet factor 4 proteins released from activated platelets. The platelet factor 4 binds to the nanoparticle surface and interacts with heparan sulfate proteoglycans on endothelial cells, and induces uptake.

Identifying cell receptors for the nanoparticle protein corona using genome screens.

Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle's surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis.

Optimizing chronic pain management through patient engagement with quality of life measures: a randomized controlled trial.

Context: Health-related quality of life (HRQOL) represents a new approach for guiding chronic pain management because it is patient-centered and more likely to be understood and accepted by patients.

Objectives: To assess the value and utility of an eHealth intervention for patients with chronic low back pain (CLBP) that was primarily based on HRQOL measures and to measure the clinical outcomes associated with its use.

Methods: A randomized controlled trial was conducted within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION Pain Research Registry) using participants screened from November 2019 through February 2021.

A review of musculoskeletal adaptations in individuals following major lower-limb amputation.

Structural musculoskeletal adaptations following amputation, such as bone mineral density (BMD) or muscle architecture, are often overlooked despite their established contributions to gait rehabilitation and the development of adverse secondary physical conditions. The purpose of this review is to provide a summary of the existing literature investigating musculoskeletal adaptations in individuals with major lower-limb amputations to inform clinical practice and provide directions for future research. Google Scholar, PubMed, and Scopus were searched for original peer-reviewed studies that included individuals with transtibial or transfemoral amputations.

Why nanoparticles prefer liver macrophage cell uptake in vivo.

Effective delivery of therapeutic and diagnostic nanoparticles is dependent on their ability to accumulate in diseased tissues. However, most nanoparticles end up in liver macrophages regardless of nanoparticle design after administration. In this review, we describe the interactions of liver macrophages with nanoparticles.

DNA-Controlled Encapsulation of Small Molecules in Protein Nanoparticles.

A nanoparticle can hold multiple types of therapeutic and imaging agents for disease treatment and diagnosis. However, controlling the storage of molecules in nanoparticles is challenging, because nonspecific intermolecular interactions are used for encapsulation. Here, we used specific DNA interactions to store molecules in nanoparticles.

A framework for designing delivery systems.

The delivery of medical agents to a specific diseased tissue or cell is critical for diagnosing and treating patients. Nanomaterials are promising vehicles to transport agents that include drugs, contrast agents, immunotherapies and gene editors. They can be engineered to have different physical and chemical properties that influence their interactions with their biological environments and delivery destinations.

Synthesis of Patient-Specific Nanomaterials.

Nanoparticles are engineered from materials such as metals, polymers, and different carbon allotropes that do not exist within the body. Exposure to these exogenous compounds raises concerns surrounding toxicity, inflammation, and immune activation. These responses could potentially be mitigated by synthesizing nanoparticles directly from molecules derived from the host.

Surface-grafted polyethylene glycol conformation impacts the transport of PEG-functionalized liposomes through a tumour extracellular matrix model.

The effect of surface PEGylation on nanoparticle transport through an extracellular matrix (ECM) is an important determinant for tumor targeting success. Fluorescent stealth liposomes (base lipid DOPC) were prepared incorporating different proportions of PEG-grafted lipids (2.5, 5 and 10% of the total lipid content) for a series of PEG molecular weights (1000, 2000 and 5000 Da).