Activated neutrophils: A next generation cellular immunotherapy.

Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype.

Immunotherapy against glioblastoma using backpack-activated neutrophils.

Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug-free disk-shaped backpacks, termed Cyto-Adhesive Micro-Patches (CAMPs) for treating GBM.

High organofluorine concentrations in municipal wastewater affect downstream drinking water supplies for millions of Americans.

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024.

Review of the environmental and health risks of hydraulic fracturing fluids.

The composition of hydraulic fracturing (HF) fluid poses risks to human health and the environment by impacting drinking water sources. Fracturing fluid recovery rate is highly variable, and the fact that a high percentage of the injected HF fluid is not produced back to the surface in some areas raises questions about its fate and possible migration into aquifers. In this paper, the composition of the HF fluid and related toxicity are described, along with insights about the environmental impact linked with HF fluid, synthesized spill data, main factors affecting the flow-back ratio, and induced seismicity related to HF activities.

A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.

While membrane proteins such as ion channels continuously turn over and require replacement, the mechanisms of specificity of efficient channel delivery to appropriate membrane subdomains remain poorly understood. GJA1-20k is a truncated Connexin43 (Cx43) isoform arising from translation initiating at an internal start codon within the same parent GJA1 mRNA and is requisite for full-length Cx43 trafficking to cell borders. GJA1-20k does not have a full transmembrane domain, and it is not known how GJA1-20k enables forward delivery of Cx43 hemichannels.

Inflammatory Bowel Disease Drivers Revealed in Human Organ Chips.

Inflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms.

Ethical considerations for biobanks serving underrepresented populations.

Biobanks are essential biological database resources for the scientific community, enabling research on the molecular, cellular, and genetic basis of human disease. They are crucial for computational, data-driven biomedical research, which advances precision medicine and the development of targeted therapies. However, biobanks often lack racial and ethnic diversity, with many data sets predominantly comprising individuals of white, primarily northern European, ancestry.

Programming liquid crystal elastomers for multistep ambidirectional deformability.

Ambidirectionality, which is the ability of structural elements to move beyond a reference state in two opposite directions, is common in nature. However, conventional soft materials are typically limited to a single, unidirectional deformation unless complex hybrid constructs are used. We exploited the combination of mesogen self-assembly, polymer chain elasticity, and polymerization-induced stress to design liquid crystalline elastomers that exhibit two mesophases: chevron smectic C (cSmC) and smectic A (SmA).

Direct visualization of relativistic quantum scars in graphene quantum dots.

Quantum scars refer to eigenstates with enhanced probability density along unstable classical periodic orbits. First predicted 40 years ago, scars are special eigenstates that counterintuitively defy ergodicity in quantum systems whose classical counterpart is chaotic. Despite the importance and long history of scars, their direct visualization in quantum systems remains an open field.

Photoinitiator-free light-mediated crosslinking of dynamic polymer and pristine protein networks.

Light-based patterning of synthetic and biological hydrogels enables precise spatial and temporal control over the formation of chemical bonds. However, photoinitiators are typically used to generate free radicals, which are detrimental to human cells. Here, we report a photoinitiator- and radical-free method based on -nitrobenzyl alcohol (NBA) photolysis, which gives rise to highly reactive nitroso and benzaldehyde groups.

Substantial Mercury Releases and Local Deposition from Permafrost Peatland Wildfires in Southwestern Alaska.

Increasing wildfire activity at high northern latitudes has the potential to mobilize large amounts of terrestrial mercury (Hg). However, understanding implications for Hg cycling and ecosystems is hindered by sparse research on peatland wildfire Hg emissions. In this study, we used measurements of soil organic carbon (SOC) and Hg, burn depth, and environmental indices derived from satellite remote sensing to develop machine learning models for predicting Hg emissions from major wildfires in the permafrost peatland of the Yukon-Kuskokwim Delta (YKD) in southwestern Alaska.

Quality control for single-cell analysis of high-plex tissue profiles using CyLinter.

Tumors are complex assemblies of cellular and acellular structures patterned on spatial scales from microns to centimeters. Study of these assemblies has advanced dramatically with the introduction of high-plex spatial profiling. Image-based profiling methods reveal the intensities and spatial distributions of 20-100 proteins at subcellular resolution in 10-10 cells per specimen.

Shape optimization for high efficiency metasurfaces: theory and implementation.

Complex non-local behavior makes designing high efficiency and multifunctional metasurfaces a significant challenge. While using libraries of meta-atoms provide a simple and fast implementation methodology, pillar to pillar interaction often imposes performance limitations. On the other extreme, inverse design based on topology optimization leverages non-local coupling to achieve high efficiency, but leads to complex and difficult to fabricate structures.

Precision game engineering through reshaping strategic payoffs.

Nash equilibrium is a key concept in game theory fundamental for elucidating the equilibrium state of strategic interactions, with applications in diverse fields such as economics, political science, and biology. However, the Nash equilibrium may not always align with desired outcomes within the broader system. This article introduces a novel game engineering framework that tweaks strategic payoffs within a game to achieve a pre-defined desired Nash equilibrium while averting undesired ones.

Characterizing the Areal Extent of PFAS Contamination in Fish Species Downgradient of AFFF Source Zones.

Most monitoring programs next to large per- and polyfluoroalkyl substances (PFAS) sources focus on drinking water contamination near source zones. However, less is understood about how these sources affect downgradient hydrological systems and food webs. Here, we report paired PFAS measurements in water, sediment, and aquatic biota along a hydrological gradient away from source zones contaminated by the use of legacy aqueous film-forming foam (AFFF) manufactured using electrochemical fluorination.

Development and Evaluation of Aquatic and Terrestrial Food Web Bioaccumulation Models for Per- and Polyfluoroalkyl Substances.

There is a need for reliable models to predict the food web bioaccumulation and assess ecological and human health risks of per- and polyfluoroalkyl substances (PFAS). This present study presents (i) the development of novel mechanistic aquatic and terrestrial food web bioaccumulation models for PFAS and (ii) an evaluation of model performance using available laboratory and field data. Model predictions of laboratory-measured bioconcentration factors and field-based bioaccumulation factors of PFAS in fish were in good agreement with observed data as measured by the mean model bias (MB), representing systematic over- or under-estimation and the standard deviation of the MB, representing general uncertainty.

Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in , we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active.

Cross-cutting studies of per- and polyfluorinated alkyl substances (PFAS) in Arctic wildlife and humans.

This cross-cutting review focuses on the presence and impacts of per- and polyfluoroalkyl substances (PFAS) in the Arctic. Several PFAS undergo long-range transport via atmospheric (volatile polyfluorinated compounds) and oceanic pathways (perfluorinated alkyl acids, PFAAs), causing widespread contamination of the Arctic. Beyond targeting a few well-known PFAS, applying sum parameters, suspect and non-targeted screening are promising approaches to elucidate predominant sources, transport, and pathways of PFAS in the Arctic environment, wildlife, and humans, and establish their time-trends.

Mitigating Metal-Organic Framework (MOF) Toxicity for Biomedical Applications.

Metal-organic frameworks (MOFs) are a novel class of crystalline porous materials, consisting of metal ions and organic linkers. These hybrid materials possess exceptional porosity and specific surface area, which have recently garnered significant interest due to their potential applications in gas separation and storage, energy storage, biomedical imaging, and drug delivery. As MOFs are being explored for biomedical applications, it is essential to comprehensively assess their toxicity.

Functional supraparticles produced by the evaporation of binary colloidal suspensions on superhydrophobic surfaces.

Hierarchically structured supraparticles can be produced by drying droplets of colloidal suspensions. Using binary suspensions provides degrees of structural and functional control beyond those possible for single components, while remaining tractable for fundamental mechanistic studies. Here, we implement evaporative co-assembly of two distinct particle types - 'large' polystyrene microparticles and 'small' inorganic oxide nanoparticles (silica, titania, zirconia, or ceria) - dried on superhydrophobic surfaces to produce bowl-shaped supraparticles.