The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of intravenously administered bacteriophage in uninfected mice.

Mechanical activation and expression of HSP27 in epithelial ovarian cancer.

Understanding the complex biomechanical tumor microenvironment (TME) is of critical importance in developing the next generation of anti-cancer treatment strategies. This is especially true in epithelial ovarian cancer (EOC), the deadliest of the gynecologic cancers due to recurrent disease or chemoresistance. However, current models of EOC progression provide little control or ability to monitor how changes in biomechanical parameters alter EOC cell behaviors.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Biomechanical stimulation promotes blood vessel growth despite VEGFR-2 inhibition.

Background: Angiogenesis, or the growth of new vasculature from existing blood vessels, is widely considered a primary hallmark of cancer progression. When a tumor is small, diffusion is sufficient to receive essential nutrients; however, as the tumor grows, a vascular supply is needed to deliver oxygen and nutrients into the increasing mass. Several anti-angiogenic cancer therapies target VEGF and the receptor VEGFR-2, which are major promoters of blood vessel development.

Multiscale simulations reveal TDP-43 molecular-level interactions driving condensation.

The RNA-binding protein TDP-43 is associated with mRNA processing and transport from the nucleus to the cytoplasm. TDP-43 localizes in the nucleus as well as accumulating in cytoplasmic condensates such as stress granules. Aggregation and formation of amyloid-like fibrils of cytoplasmic TDP-43 are hallmarks of numerous neurodegenerative diseases, most strikingly present in >90% of amyotrophic lateral sclerosis (ALS) patients.

Classification and Simulation of Structural Phase Transformation-Induced Interfacial Defects in Group VI Transition-Metal Dichalcogenide Monolayers.

Polymorphic 2D materials have recently emerged as promising candidates for use in nanoelectronic devices by way of their ability to undergo structural phase transformations induced by external fields. Under cyclic transformations, however, induced interfacial defects may proliferate and compromise the system properties. Herein, we first employ geometric analysis to classify such defects generated during the 2H ↔ 1T and 2H ↔ 1T' transformations in group VI transition-metal dichalcogenide monolayers.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Bacteriophage genome engineering with CRISPR-Cas13a.

Jumbo phages such as Pseudomonas aeruginosa ФKZ have potential as antimicrobials and as a model for uncovering basic phage biology. Both pursuits are currently limited by a lack of genetic engineering tools due to a proteinaceous 'phage nucleus' structure that protects from DNA-targeting CRISPR-Cas tools. To provide reverse-genetics tools for DNA jumbo phages from this family, we combined homologous recombination with an RNA-targeting CRISPR-Cas13a enzyme and used an anti-CRISPR gene (acrVIA1) as a selectable marker.

Modeling of Human Neuroendocrine Tumors in Tissue Surrogates.

Few models exist for studying neuroendocrine tumors (NETs), and there are mounting concerns that the currently available array of cell lines is not representative of NET biology. The lack of stable patient-derived NET xenograft models further limits the scientific community's ability to make conclusions about NETs and their response to therapy in patients. To address these limitations, we propose the use of an ex vivo 3D flow-perfusion bioreactor system for culturing and studying patient-derived NET surrogates.

Utilization of a 3-D tissue engineered model to investigate the effects of perfusion on gynecologic cancer biology.

Among gynecologic malignancies, ovarian cancer (OC) has the poorest survival rate, and its clinical management remains challenging due to the high rate of recurrence and chemoresistance. Improving survival for these patients is critical, although this requires the ability to translate preclinical studies to actual patient care: bench to bedside and back. Our objective was to develop a preclinical model that accurately represents tumor biology and its microenvironment.

Local SARS-CoV-2 Peptide-Specific Immune Responses in Lungs of Convalescent and Uninfected Human Subjects.

Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovering from COVID-19 (COVID-19 ) are beginning to be appreciated; but little is known about lung resident memory T cells (lung TRM) in SARS-CoV-2 infection. Here, we utilize a perfused three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 proteins in lung tissues.

Bioreactor Suspension Culture: Differentiation and Production of Cardiomyocyte Spheroids From Human Induced Pluripotent Stem Cells.

Human induced-pluripotent stem cells (hiPSCs) can be efficiently differentiated into cardiomyocytes (hiPSC-CMs) via the GiWi method, which uses small-molecule inhibitors of glycogen synthase kinase (GSK) and tankyrase to first activate and then suppress Wnt signaling. However, this method is typically conducted in 6-well culture plates with two-dimensional (2D) cell sheets, and consequently, cannot be easily scaled to produce the large numbers of hiPSC-CMs needed for clinical applications. Cell suspensions are more suitable than 2D systems for commercial biomanufacturing, and suspended hiPSCs form free-floating aggregates (i.

Three-Dimensionally Printed Skin Substitute Using Human Dermal Fibroblasts and Human Epidermal Keratinocytes.

Introduction: Wound healing affects millions of people annually. After injury, keratinocytes from the wound edge proliferate, migrate, and differentiate to recapitulate the 3-dimensional (3D) structure needed to provide a barrier function. If the wound is too large, skin grafting may be required.

Defect-Enabled Phase Programming of Transition Metal Dichalcogenide Monolayers.

The ability to tune the local electronic transport properties of group VI transition metal dichalcogenide (TMD) monolayers by strain-induced structural phase transformations ("phase programming") has stimulated much interest in the potential applications of such layers as ultrathin programmable and dynamically switchable nanoelectronics components. In this manuscript, we propose a new approach toward controlling TMD monolayer phases by employing macroscopic in-plane strains to amplify heterogeneous strains arising from tailored, spatially extended defects within the monolayer. The efficacy of our proposed approach is demonstrated via numerical simulations of emerging domains localized around arrays of holes, grain boundaries, and compositional heterointerfaces.

Extracellular Vesicle Mediated Tumor-Stromal Crosstalk Within an Engineered Lung Cancer Model.

Tumor-stromal interactions within the tumor microenvironment (TME) influence lung cancer progression and response to therapeutic interventions, yet traditional studies fail to replicate the complexity of these interactions. Herein, we developed three-dimensional (3D) lung tumor models that mimic the human TME and demonstrate tumor-stromal crosstalk mediated by extracellular vesicles (EVs). EVs released by tumor cells, independent of p53 status, and fibroblasts within the TME mediate immunomodulatory effects; specifically, monocyte/macrophage polarization to a tumor-promoting M2 phenotype within this 3D-TME.

Layer-By-Layer Fabrication of Large and Thick Human Cardiac Muscle Patch Constructs With Superior Electrophysiological Properties.

Engineered cardiac tissues fabricated from human induced pluripotent stem cells (hiPSCs) show promise for ameliorating damage from myocardial infarction, while also restoring function to the damaged left ventricular (LV) myocardium. For these constructs to reach their clinical potential, they need to be of a clinically relevant volume and thickness, and capable of generating synchronous and forceful contraction to assist the pumping action of the recipient heart. Design prerequisites include a structure thickness sufficient to produce a beneficial contractile force, prevascularization to overcome diffusion limitations and sufficient structural development to allow for maximal cell communication.

A compact Cascade-Cas3 system for targeted genome engineering.

CRISPR-Cas technologies have enabled programmable gene editing in eukaryotes and prokaryotes. However, the leading Cas9 and Cas12a enzymes are limited in their ability to make large deletions. Here, we used the processive nuclease Cas3, together with a minimal Type I-C Cascade-based system for targeted genome engineering in bacteria.

Fabrication and characterization of a thick, viable bi-layered stem cell-derived surrogate for future myocardial tissue regeneration.

Cardiac tissue surrogates show promise for restoring mechanical and electrical function in infarcted left ventricular (LV) myocardium. For these cardiac surrogates to be useful, they are required to support synchronous and forceful contraction over the infarcted region. These design requirements necessitate a thickness sufficient to produce a useful contractile force, an area large enough to cover an infarcted region, and prevascularization to overcome diffusion limitations.

Mechanical strain induces phenotypic changes in breast cancer cells and promotes immunosuppression in the tumor microenvironment.

Breast cancer (BCa) proliferates within a complex, three-dimensional microenvironment amid heterogeneous biochemical and biophysical cues. Understanding how mechanical forces within the tumor microenvironment (TME) regulate BCa phenotype is of great interest. We demonstrate that mechanical strain enhanced the proliferation and migration of both estrogen receptor and triple-negative (TNBC) human and mouse BCa cells.

Large-area epitaxial growth of curvature-stabilized ABC trilayer graphene.

The properties of van der Waals (vdW) materials often vary dramatically with the atomic stacking order between layers, but this order can be difficult to control. Trilayer graphene (TLG) stacks in either a semimetallic ABA or a semiconducting ABC configuration with a gate-tunable band gap, but the latter has only been produced by exfoliation. Here we present a chemical vapor deposition approach to TLG growth that yields greatly enhanced fraction and size of ABC domains.

A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases.

All viruses require strategies to inhibit or evade the immune pathways of cells that they infect. The viruses that infect bacteria, bacteriophages (phages), must avoid immune pathways that target nucleic acids, such as CRISPR-Cas and restriction-modification systems, to replicate efficiently. Here we show that jumbo phage ΦKZ segregates its DNA from immunity nucleases of its host, Pseudomonas aeruginosa, by constructing a proteinaceous nucleus-like compartment.

The MoSeS dynamic omnigami paradigm for smart shape and composition programmable 2D materials.

The properties of 2D materials can be broadly tuned through alloying and phase and strain engineering. Shape programmable materials offer tremendous functionality, but sub-micron objects are typically unachievable with conventional thin films. Here we propose a new approach, combining phase/strain engineering with shape programming, to form 3D objects by patterned alloying of 2D transition metal dichalcogenide (TMD) monolayers.

Accelerating Clinical Innovation in Biomedical Engineering Education by Using a Digital Portal for Collaboration.

The rapidly changing healthcare landscape requires continuous innovation by clinicians, yet generating ideas to improve patient care is often problematic. This paper describes the development of a digital tool used in an interprofessional program designed to enhance collaborations between clinicians, undergraduate, and graduate STEM students, particularly biomedical engineering (BME). The program founders began by connecting clinicians and students through a course portal in a learning management system (LMS).

Correction: Maturation of three-dimensional, hiPSC-derived cardiomyocyte spheroids utilizing cyclic, uniaxial stretch and electrical stimulation.

[This corrects the article DOI: 10.1371/journal.pone.