Liquid-based encapsulation for implantable bioelectronics across broad pH environments.

Wearable and implantable bioelectronics that can interface for extended periods with highly mobile organs and tissues across a broad pH range would be useful for various applications in basic biomedical research and clinical medicine. The encapsulation of these systems, however, presents a major challenge, as such devices require superior barrier performance against water and ion penetration in challenging pH environments while also maintaining flexibility and stretchability to match the physical properties of the surrounding tissue. Current encapsulation materials are often limited to near-neutral pH conditions, restricting their application range.

Emerging insights into the impact of systemic metabolic changes on tumor-immune interactions.

Tumors are inherently embedded in systemic physiology, which contributes metabolites, signaling molecules, and immune cells to the tumor microenvironment. As a result, any systemic change to host metabolism can impact tumor progression and response to therapy. In this review, we explore how factors that affect metabolic health, such as diet, obesity, and exercise, influence the interplay between cancer and immune cells that reside within tumors.

Associations of Voice Metrics with Postural Function in Parkinson's Disease.

Background: This study aimed to explore the potential associations between voice metrics of patients with PD and their motor symptoms.

Methods: Motor and vocal data including the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Harmonic-Noise Ratio (HNR), jitter, shimmer, and smoothed cepstral peak prominence (CPPS) were analyzed through exploratory correlations followed by univariate linear regression analyses. We employed these four voice metrics as independent variables and the total and sub-scores of the UPDRS-III as dependent variables.

Decoding Codon Bias: The Role of tRNA Modifications in Tissue-Specific Translation.

The tRNA epitranscriptome has been recognized as an important player in mRNA translation regulation. Our knowledge of the role of the tRNA epitranscriptome in fine-tuning translation via codon decoding at tissue or cell levels remains incomplete. We analyzed tRNA expression and modifications as well as codon optimality across seven mouse tissues.

The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in .

toxigenic strains represent a critical health threat, mainly due to their link to antibiotic-associated hemorrhagic colitis. This serious condition results from the bacteria's ability to produce tilimycin and tilivalline cytotoxins. Our research highlights the pivotal role of OmpR, a key regulator within the EnvZ/OmpR two-component system, in controlling the virulence factors associated with .

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.

Human naïve B cells recognize prepandemic influenza virus hemagglutinins.

Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as the highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this naïve repertoire and the possibility to respond to emerging, prepandemic viruses are largely undetermined. Here, we profiled naïve B cell reactivity against a prototypical HPAI H5 hemagglutinin (HA), the major target of antibody responses.

Bioprinted optoelectronically active cardiac tissues.

Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation-induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light.

Automating alloy design and discovery with physics-aware multimodal multiagent AI.

The design of new alloys is a multiscale problem that requires a holistic approach that involves retrieving relevant knowledge, applying advanced computational methods, conducting experimental validations, and analyzing the results, a process that is typically slow and reserved for human experts. Machine learning can help accelerate this process, for instance, through the use of deep surrogate models that connect structural and chemical features to material properties, or vice versa. However, existing data-driven models often target specific material objectives, offering limited flexibility to integrate out-of-domain knowledge and cannot adapt to new, unforeseen challenges.

Biodegradable polymeric microsphere formulations of full-length anti-VEGF antibody bevacizumab for sustained intraocular delivery.

Age-related macular degeneration (AMD) is one of the leading causes of central vision loss in the elderly population. Bevacizumab, a full-length humanized monoclonal anti-VEGF antibody, is commonly used off-label drug to treat AMD. However, the dosing regimen of bevacizumab and other anti-VEGF antibodies requires monthly intravitreal injections followed by regular intravitreal injections at 4-16-week intervals.

Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults.

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine.

Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.

Biological and Social Predictors of HIV-1 RNA Viral Suppression in ART Treated PWLH in Sub-Saharan Africa.

HIV remains a significant health issue, especially in sub-Saharan Africa. There are 39 million people living with HIV (PLWH) globally. Treatment with ART improves patient outcomes by suppressing the HIV RNA viral load.

Maximizing Free Energy Gain.

Maximizing the amount of work harvested from an environment is important for a wide variety of biological and technological processes, from energy-harvesting processes such as photosynthesis to energy storage systems such as fuels and batteries. Here, we consider the maximization of free energy-and by extension, the maximum extractable work-that can be gained by a classical or quantum system that undergoes driving by its environment. We consider how the free energy gain depends on the initial state of the system while also accounting for the cost of preparing the system.

The perceptual primacy of feeling: Affectless visual machines explain a majority of variance in human visually evoked affect.

Looking at the world often involves not just seeing things, but feeling things. Modern feedforward machine vision systems that learn to perceive the world in the absence of active physiology, deliberative thought, or any form of feedback that resembles human affective experience offer tools to demystify the relationship between seeing and feeling, and to assess how much of visually evoked affective experiences may be a straightforward function of representation learning over natural image statistics. In this work, we deploy a diverse sample of 180 state-of-the-art deep neural network models trained only on canonical computer vision tasks to predict human ratings of arousal, valence, and beauty for images from multiple categories (objects, faces, landscapes, art) across two datasets.

Engineering of a lysosomal-targeted GAA enzyme.

Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme.

Novel Integration of Spatial and Single-Cell Omics Data Sets Enables Deeper Insights into IPF Pathogenesis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, particularly local fibrosis centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) transcriptomics and adopted the Query method and the Overlap method to determine cell type enrichments in histopathological regions.

Accuracy of privacy preserving record linkage for real world data in the United States: a systemic review.

Objectives: Examine the accuracy of privacy preserving record linkage (PPRL) matches in real world data (RWD).

Materials And Methods: We conducted a systematic literature review to identify articles evaluating PPRL methods from January 1, 2013 to June 15, 2023. Eligible studies included original research reporting quantitative metrics such as precision and recall in health-related data sources.

Defects vibrations engineering for enhancing interfacial thermal transport in polymer composites.

To push upper boundaries of thermal conductivity in polymer composites, understanding of thermal transport mechanisms is crucial. Despite extensive simulations, systematic experimental investigation on thermal transport in polymer composites is limited. To better understand thermal transport processes, we design polymer composites with perfect fillers (graphite) and defective fillers (graphite oxide), using polyvinyl alcohol (PVA) as a matrix model.

Influences of fluctuating nutrient loadings on nitrate-reducing microorganisms in rivers.

Rivers serve important functions for human society and are significantly impacted by anthropogenic nutrient inputs (e.g. organic and sulfur compounds).

Protein quality control is a master modulator of molecular evolution in bacteria.

The bacterial protein quality control (PQC) network comprises a set of genes that promote proteostasis (proteome homeostasis) through proper protein folding and function via chaperones, proteases, and a protein translational machinery. It participates in vital cellular processes and influences organismal development and evolution. In this review, we examine the mechanistic bases for how the bacterial PQC network influences molecular evolution.

Impact of lesion preparation-induced calcified plaque defects in vascular intervention for atherosclerotic disease: in silico assessment.

Percutaneous coronary interventions in highly calcified atherosclerotic lesions are challenging due to the high mechanical stiffness that significantly restricts stent expansion. Intravascular lithotripsy (IVL) is a novel vessel preparation technique with the potential to improve interventional outcomes by inducing microscopic and macroscopic cracks to enhance stent expansion. However, the exact mechanism of action for IVL is poorly understood, and it remains unclear whether the improvement in-stent expansion is caused by either the macro-cracks allowing the vessel to open or the micro-cracks altering the bulk material properties.

A Microphysiological Model of Progressive Human Hepatic Insulin Resistance.

Background & Aims: Hepatic insulin resistance is a fundamental phenomenon observed in both Type 2 diabetes (T2D) and metabolic (dysfunction) associated fatty liver disease (MAFLD). The relative contributions of nutrients, hyperinsulinemia, hormones, inflammation, and other cues are difficult to parse as they are convoluted by interplay between the local and systemic events. Here, we used a well-established human liver microphysiological system (MPS) to establish a physiologically-relevant insulin-responsive metabolic baseline and probe how primary human hepatocytes respond to controlled perturbations in insulin, glucose, and free fatty acids (FFAs).

State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.

In the later stages of Parkinson's disease (PD), patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine (DA) during dyskinesia were characterized using electrophysiological, pharmacological, molecular and behavioral approaches.

Schedule optimization for chemical library synthesis.

Automated chemistry platforms hold the potential to enable large-scale organic synthesis campaigns, such as producing a library of compounds for biological evaluation. The efficiency of such platforms will depend on the schedule according to which the synthesis operations are executed. In this work, we study the scheduling problem for chemical library synthesis, where operations from interdependent synthetic routes are scheduled to minimize the makespan-the total duration of the synthesis campaign.

Autonomous Self-Healing Magnetoelectric I-Skin from Self-Bonded Deep Eutectic Polymer.

Next-generation ionic skin (i-skin) should be self-healing and self-powered, promoting its development toward lightweight, miniaturization, compact, and portable designs. Previously reported self-powered i-skin mostly either lack the ability to self-repair damaged parts or only have self-healing capabilities some components, falling short of achieving complete device self-healability. In this work, a self-bonding strategy is presented to obtain an all-polymerizable deep eutectic solvent (PDES) magnetoelectric i-skin (MIS) that simultaneously achieves self-powering and full-device autonomous self-healability.