Biomimetic Anisotropic-Functionalized Platelet-Membrane-Coated Polymeric Particles for Targeted Drug Delivery to Human Breast Cancer Cells.

Biomimetic particles that can replicate aspects of natural biological cell function are useful for advanced biological engineering applications. Engineering such particles requires mimicking the chemical complexity of the surface of biological cells, and this can be achieved by coating synthetic particles with naturally derived cell membranes. Past research has demonstrated the feasibility of utilizing cell membrane coatings from a variety of cell types to achieve extended blood circulation half-life.

Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy.

Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural antigen presenting cells in order to stimulate T cells in an antigen-specific manner using an acellular platform. We have engineered an enhanced nanoscale biodegradable artificial antigen presenting cell by modulating particle shape to achieve a nanoparticle geometry that allows for increased radius of curvature and surface area for T cell contact. The non-spherical nanoparticle artificial antigen presenting cells developed here have reduced nonspecific uptake and improved circulation time compared both to spherical nanoparticles and to traditional microparticle technologies.

Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass in the local Universe.

A scalable and robust cationic lipid/polymer hybrid nanoparticle platform for mRNA delivery.

mRNA based gene therapies hold the potential to treat multiple diseases with significant advantages over DNA based therapies, including rapid protein expression and minimized risk of mutagenesis. However, successful delivery of mRNA remains challenging, and clinical translation of mRNA therapeutics has been limited. This study investigated the use of a lipid/polymer hybrid (LPH) nanocarrier for mRNA, designed to address key delivery challenges and shuttle mRNA to targeted tissues.

Hutch++: Optimal Stochastic Trace Estimation.

We study the problem of estimating the trace of a matrix that can only be accessed through matrix-vector multiplication. We introduce a new randomized algorithm, Hutch++, which computes a (1 ± ) approximation to tr( ) for any positive semidefinite (PSD) using just (1) matrix-vector products. This improves on the ubiquitous , which requires (1 ) matrix-vector products.

The impact of statin therapy and aerobic exercise training on skeletal muscle and whole-body aerobic capacity.

Background: Statin use is widely recognized for improving cardiovascular health, but questions remain on how statin use influences skeletal muscle, particularly mitochondrial function.

Study Objective Design And Participants: The influence of statin therapy and exercise (EX) on aerobic capacity was determined. In Study1, skeletal muscle aerobic capacity was measured before and after 80 mg atorvastatin therapy.

Microsurgical Repair of Inferior Alveolar Nerve Injuries Associated With Endodontic Treatment: Results on Sensory Function and Relief of Pain.

Purpose: An uncommon, but serious complication of endodontic treatment is inferior alveolar nerve (IAN) injury warranting operative intervention for exploration, debridement, and repair. The purpose of the study was to evaluate outcomes of microneurosurgical intervention for endotontic-related IAN injuries in terms of achievement of functional sensory recovery (FSR) and pain relief and to identify factors affecting outcomes.

Methods: A retrospective cohort study of patients who had microsurgical exploration and repair of IAN injuries sustained during endodontic therapy was performed.

How Many Oral Surgeons Does It Take to Classify a Nerve Injury?

Purpose: There is inconsistency in clinical grading of peripheral trigeminal nerve (TN5) injuries that impact patient care. The study goal is to assess the current status of evaluation and classification of TN5 injuries by oral and maxillofacial surgeons (OMSs).

Patients And Methods: A cross-sectional study design used an electronic survey to 100 selected OMSs to determine their clinical TN5 injury practice, including neurosensory testing, confidence level with current protocols, and evaluation and treatment of a hypothetical TN5 injury case.

Biodegradable Cationic Polymer Blends for Fabrication of Enhanced Artificial Antigen Presenting Cells to Treat Melanoma.

Biomimetic biomaterials are being actively explored in the context of cancer immunotherapy because of their ability to directly engage the immune system to generate antitumor responses. Unlike cellular therapies, biomaterial-based immunotherapies can be precisely engineered to exhibit defined characteristics including biodegradability, physical size, and tuned surface presentation of immunomodulatory signals. In particular, modulating the interface between the biomaterial surface and the target biological cell is key to enabling biological functions.

Incidence of Pre-Existing Lingual Cortex Perforation Before Removal of Mandibular Third Molars.

Purpose: The objective of this study was to determine the relationship between the mandibular third molar tooth (Md3) and the adjacent lingual cortical bone and determine the incidence of lingual cortex perforation by Md3s.

Patients And Methods: This retrospective study was designed and implemented from 100 cone-beam computed tomographic scans (CBCTs) of patients with age ranging from 18 to 65 years old. The primary outcome was to assess the incidence of mandibular third molars (Md3s) with existing lingual cortex perforation by their roots.

Biomimetic tolerogenic artificial antigen presenting cells for regulatory T cell induction.

Regulatory T cell (Treg)-based therapeutics are receiving increased attention for their potential to treat autoimmune disease and prevent transplant rejection. Adoptively transferred Tregs have shown promise in early clinical trials, but cell-based therapies are expensive and complex to implement, and "off-the-shelf" alternatives are needed. Here, we investigate the potential of artificial antigen presenting cells (aAPCs) fabricated from a blend of negatively charged biodegradable polymer (poly(lactic-co-glycolic acid), PLGA) and cationic biodegradable polymer (poly(beta-amino ester), PBAE) with incorporation of extracellular protein signals 1 and 2 and a soluble released signal 3 to convert naïve T cells to induced Foxp3+ Treg-like suppressor cells (iTregs) both in vitro and in vivo in a biomimetic manner.

Biomimetic anisotropic polymeric nanoparticles coated with red blood cell membranes for enhanced circulation and toxin removal.

The design of next-generation nanobiomaterials requires precise engineering of both physical properties of the core material and chemical properties of the material's surface to meet a biological function. A bio-inspired modular and versatile technology was developed to allow biodegradable polymeric nanoparticles to circulate through the blood for extended periods of time while also acting as a detoxification device. To mimic red blood cells, physical and chemical biomimicry are combined to enhance the biological function of nanomaterials in vitro and in vivo.

In situ genetic engineering of tumors for long-lasting and systemic immunotherapy.

Cancer immunotherapy has been the subject of extensive research, but highly effective and broadly applicable methods remain elusive. Moreover, a general approach to engender endogenous patient-specific cellular therapy, without the need for a priori knowledge of tumor antigen, ex vivo cellular manipulation, or cellular manufacture, could dramatically reduce costs and broaden accessibility. Here, we describe a biotechnology based on synthetic, biodegradable nanoparticles that can genetically reprogram cancer cells and their microenvironment in situ so that the cancer cells can act as tumor-associated antigen-presenting cells (tAPCs) by inducing coexpression of a costimulatory molecule (4-1BBL) and immunostimulatory cytokine (IL-12).

Aerobic Exercise Improves Microvascular Function in Older Adults.

Unlabelled: Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease.

Purpose: The study aimed to assess changes in peripheral microvascular function in sedentary older adults after aerobic exercise training.

Effects of altered pyruvate dehydrogenase activity on contracting skeletal muscle bioenergetics.

During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads.

Polymeric micro- and nanoparticles for immune modulation.

New advances in biomaterial-based approaches to modulate the immune system are being applied to treat cancer, infectious diseases, and autoimmunity. Particulate systems are especially well-suited to deliver immunomodulatory factors to immune cells since their small size allows them to engage cell surface receptors or deliver cargo intracellularly after internalization. Biodegradable polymeric particles are a particularly versatile platform for the delivery of signals to the immune system because they can be easily surface-modified to target specific receptors and engineered to release encapsulated cargo in a precise, sustained manner.

Fabrication of Anisotropic Polymeric Artificial Antigen Presenting Cells for CD8+ T Cell Activation.

Artificial antigen presenting cells (aAPC) are a promising platform for immune modulation due to their potent ability to stimulate T cells. Acellular substrates offer key advantages over cell-based aAPC, including precise control of signal presentation parameters and physical properties of the aAPC surface to modulate its interactions with T cells. aAPC constructed from anisotropic particles, particularly ellipsoidal particles, have been shown to be more effective than their spherical counterparts at stimulating T cells due to increased binding and larger surface area available for T cell contact, as well as reduced nonspecific uptake and enhanced pharmacokinetic properties.