Factors influencing monoclonal antibody pharmacokinetics across varying immune perturbations.

The development of continuous-release devices or injectables for the long-term delivery of biologics is of great interest, especially monoclonal antibodies (mAbs) that require frequent, high-dose injections. Preclinical testing of these technologies in murine models is necessary for clinical translation; however, xenogeneic responses to the mAb and foreign body responses to the implants or injectables can confound results. Immune system knockout (KO) models that affect immune cells are often used in these experiments, but the effects of KO models on mAb pharmacokinetics (PK) are not well characterized.

Plectin affects cell viscoelasticity at small and large deformations.

Plectin is a giant protein of the plakin family that crosslinks the cytoskeleton of mammalian cells. It is expressed in virtually all tissues and its dysfunction is associated with various diseases such as skin blistering. There is evidence that plectin regulates the mechanical integrity of the cytoskeleton in diverse cell and tissue types.

Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System.

The enteric nervous system (ENS) is the intrinsic nervous system of the gut and controls essential functions, such as gut motility, intestinal barrier function, and water balance. The ENS displays a complex 3D architecture within the context of the gut and specific transcriptional states needed to control gut homeostasis. During development, the ENS develops from enteric neural progenitor cells (ENPs) that migrate into the gut and differentiate into functionally diverse neuron types.

A multimodal approach to assess a liposomal carrier's biodistribution, stability, and clearance.

Liposomal carriers, used for site-specific drug delivery, are being investigated for diagnostic approaches by replacing the therapeutic with an imaging contrast agent, exploring potential for selective treatment planning. There remains a critical need to improve assessment of biodistribution, stability, and clearance kinetics of liposomal carriers. This pilot study presents a multimodal approach in which liposome-encapsulated J-aggregated indocyanine green (ICG) dye (Lipo-JICG) is imaged with high spatial resolution using both photoacoustic (PA) imaging, to assess the absorbance characteristics of JICG and monomeric ICG, and cryofluorescence tomography (CFT), to measure ICG fluorescence.

Emerging infectious disease outbreaks and real-time health communication: intermediality, uncertainty and dissent.

This article maps out the challenges of public global health communication in the context of the COVID-19 pandemic by providing an overview of the shifting media of health communication from the post-Second World War era to the present. The article explores the communication of science in real-time or live media of film, television, video and digital social media during three emerging infectious-disease (EID) outbreaks to place COVID-19 health communication in historical perspective. Examination of the transition from centralized, top-down communications to distributed, many-to-many, mobile communication illuminates challenges to expertise, authority and control of health narratives and imagery.

Pharmacogenomics of buprenorphine - a narrative review.

Buprenorphine, a semi-synthetic opioid, is used to treat Opioid Use Disorder (OUD) and as an analgesic. Buprenorphine's benefits over other opioids include longer duration of action, lower abuse potential, and a ceiling effect to serious adverse effects such as respiratory depression. This is a literature review of gene variants affecting the pharmacokinetics and pharmacodynamics of buprenorphine from databases, such as PubMed.

Thermal responses of feeding rates differ across co-occurring predator species.

Changes in global temperature regimes are expected to transform species interactions in natural communities. However, predicting the consequences of warming on populations and communities is challenging because species interact with a range of community members. In theory, species should be adapted to their local temperature regimes, which might suggest a parallel shift across species interactions.

in Texas: A Contemporary One Health Scoping Review of Vectors, Reservoirs, and Human Health.

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to .

The lab-field continuum in conservation physiology research: leveraging multiple approaches to inform policy and practice.

In the field of conservation physiology, there is often a trade off between conducting research in controlled laboratory settings or in inherently variable field environments. However, this belief sets up a false dichotomy where laboratory experiments are perceived as providing precise, mechanistic understanding with low variability at the cost of environmental realism while field studies are ecologically relevant but criticized for generating inconsistent evidence that is difficult to interpret and replicate. Despite the perceived binary view, these approaches are not in opposition to one another, but rather form a continuum along increasing ecological complexity.

Local Delivery of Non-opioid Analgesic Microparticles to Modulate Post-surgical Pain.

Purpose: Postsurgical pain (PSP) is a common complication in surgical patients that can progress to chronic pain and opioid dependence. Current analgesics, including opioids and non-opioid agents, are limited by short durations of action and adverse effects. This study reports the development and evaluation of extended-release bupivacaine microparticles (BuMPs) designed to provide sustained local analgesia and improve post-surgical pain management.

An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.

is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small-molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluated the preclinical efficacy of BI-2493, a first-in-class allele-agnostic mutant-KRAS inhibitor (panKRASi), in pancreatic ductal adenocarcinoma (PDAC).

Quantification method affects replicability of eQTL analysis, colocalization, and TWAS.

eQTL mapping and TWAS are widely used to contextualize GWAS, yet the impact of RNA-seq processing choices remains unexplored. We find that RNA-seq quantification method and transcriptomic reference substantially affect eQTL detection and gene expression prediction with significant downstream impact on colocalization and TWAS results. Our findings demonstrate that seemingly minor methodological decisions substantially affect these common analyses, highlighting the need for standardized practices to ensure reproducible genetic association studies.

Microbicidal mechanisms for light-activated molecular nanomachines in : A model for pathogenic bacteria.

There is a global health crisis of antimicrobial resistance, responsible for over a million deaths annually. Mycobacterial infections are a major contributor to this crisis, causing more deaths than any other single infectious agent. Notably, the rise of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains of has led to higher mortality rates and challenge all existing antibiotic regimens.

The MCTOT app: A publicly available tool for statistical cycle-to-threshold analysis and inference of informative but uncertainly determined qPCR data.

As a common experimental technique, qPCR (Quantitative Real-time Polymerase Chain Reaction) is widely used to measure levels of nucleic acids, e.g., microRNAs and messenger RNA.

Critical Role of Mg Ions in RNA Folding Transitions: Anchoring the A-Minor Twist in the SAM-II Riboswitch.

Magnesium ions (Mg) play a crucial role in stabilizing various RNA tertiary motifs, such as pseudoknots, G-quadruplexes, kissing loops, and A-minor motifs, to name a few. Despite their importance, the precise location and role of Mg ions in RNA folding are challenging to characterize both experimentally and computationally. In this study, we employ an all-atom structure-based model integrated with the dynamic counterion condensation (DCC) model to investigate the folding and unfolding transitions of apo SAM-II riboswitch RNA at physiological concentrations of Mg.

Ultrahigh pressure compaction-resistant thin film crosslinked composite reverse osmosis membranes.

In this study, we present a class of thin-film crosslinked (TFX) composite reverse osmosis (RO) membranes that resist physical compaction at ultrahigh pressures (up to 200 bar). Since RO membranes experience compaction at virtually all pressure ranges, the ability to resist compaction has widespread implications for RO membrane technology. The process described herein involves crosslinking a phase inverted porous polyimide (PI) support membrane followed by interfacial polymerization of a polyamide layer, thereby forming a fully thermoset composite membrane structure.

A Statistical Summary and Visualization Tool for a 30-year Background Soil and Sediment Metals Data from North Carolina Superfund Sites.

The remediation of Comprehensive Environmental Response, Compensation, and Liability Act or Superfund sites is limited to cleanup to levels no lower than background concentrations. However, both anthropogenically induced and naturally occurring metal concentrations in soil and sediments often complicate this cleanup process. To support informed decisions on heavy metal cleanup and the development of soil heavy metal-related policies in North Carolina, a statewide dataset of background heavy metal data from Superfund site investigations was compiled.

Spatial Control of Optical Emission and Conductivity in Molybdenum Oxide through Electron-Beam Irradiation.

Deterministic spatial control of material properties is essential for advanced electronic and optoelectronic device technologies. van der Waals (vdW) materials stand out for their high tunability, yet achieving multifunctional on-chip control remains challenging. Here, we focus on α-MoO and site-selectively modulate both its optical emission and conductivity via electron-beam irradiation.

Analysis and management of thermal loads generated in vivo by miniaturized optoelectronic implantable devices.

Miniaturized implantable optoelectronic technologies for in vivo biomedical applications are gaining interest, but require strict thermal management for safe operation. Here, we introduce a comprehensive framework combining analytical solutions and numerical modeling to estimate and manage thermal effects of optoelectronic devices. We propose Green's functions to analytically solve temperature distributions in tissue from a point source with coupled thermal-optical power, capturing the influence of critical tissue properties and spatiotemporal parameters.

SCREEN: SCatteREr ENabled optical asymmetry.

Optics that allow us to see clearly along one viewing direction while obscuring others' view of us are useful in numerous settings, including privacy-preserving window screens and one-way mirrors for psychological studies. Additionally, due to the rise of cameras that are able to see outside the visible spectrum, there is a need for optics that can also provide one-way visibility at these wavelengths. This is particularly challenging for thermal (i.

Deciphering transcriptomic changes in chemobrain: a comprehensive review.

Chemotherapy-induced cognitive impairments (CICI), colloquially known as "chemobrain," represents a profound and debilitating side effect experienced by a significant number of cancer survivors, impacting their memory, multitasking, and quality of life. This review critically evaluates the molecular mechanisms underlying CICI, with a particular focus on the insights gained from transcriptomic analyses. As cancer incidence rises globally, understanding the complex interplay between chemotherapy agents and their cognitive repercussions becomes increasingly vital.

Non-equilibrium critical scaling and universality in a quantum simulator.

Universality and scaling laws are hallmarks of equilibrium phase transitions and critical phenomena. However, extending these concepts to non-equilibrium systems is an outstanding challenge. Despite recent progress in the study of dynamical phases, the universality classes and scaling laws for non-equilibrium phenomena are far less understood than those in equilibrium.

Probiotic acoustic biosensors for noninvasive imaging of gut inflammation.

Inflammatory bowel diseases (IBD) affect millions of people globally, result in severe symptoms, and are difficult to diagnose and monitor - often necessitating the use of invasive and costly methods such as colonoscopies or endoscopies. Engineered gut bacteria offer a promising alternative due to their ability to persist in the gastrointestinal (GI) tract and sense and respond to specific environmental signals. However, probiotics that have previously been engineered to report on inflammatory and other disease biomarkers in the Gl tract rely on fluorescent or bioluminescent reporters, whose signals cannot be resolved in situ due to the poor penetration of light in tissue, or on colorimetric reporters which rely on plating feces.

Delivery of cytokines via encapsulated human astrocytes for neural immunomodulation.

Modulating neuroinflammation with biomaterial advancements has potential for restoring normative function in a wide variety of neuropathologic conditions. Because astrocytes dynamically react to the microenvironment and contribute to the neuroinflammatory process, they are well situated as initiators and/or targets for biomaterial-based immunomodulation strategies. To achieve this, we devised and validated an alginate hydrogel encapsulation approach using human pluripotent stem cell-derived astrocytes that enabled a novel coculture system with organoids composed of neurons, astrocytes, and microglia.

Development of Silk Fibroin-Based Sponges Loaded with LL-37-Derived Peptides for the Control of Orthopedic Infections.

species are often the cause of implant-related infections, posing a significant clinical challenge in orthopedics. Antimicrobial peptides (AMPs) like LL-37-derived FK-16 and GF-17 offer promising alternatives to conventional antibiotics; however, they require suitable delivery systems to overcome rapid degradation. The aim of this study was to develop and evaluate silk fibroin (SF) and osteoinductive peptide-enriched silk fibroin (PSF) sponges that can be used locally for FK-16 and GF-17 delivery.