Targeted CRISPR/Cas9 Lipid Nanoparticles Elicits Therapeutic Genome Editing in Head and Neck Cancer.

Squamous cell carcinomas of the head and neck (HNSCC) originate in the upper aerodigestive tract, including the oral cavity, pharynx, and larynx. Current treatments of locally advanced HNSCC often lead to high treatment failure, and disease recurrence, resulting in poor survival rates. Advances in mRNA technologies and lipid nanoparticle (LNP) delivery systems led to several clinical trials involving LNP-CRISPR-Cas9 mRNA-based therapeutics.

Lipid Nanoparticles With Fine-Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics.

Lipid Nanoparticles (LNPs) recently emerged as an invaluable RNA delivery platform. With many LNP-based therapeutics in the pre-clinical and clinical pipelines, there is extensive research dedicated to improving LNPs. These efforts focus mainly on the tolerability and transfectability of new ionizable lipids and RNAs, or modulating LNPs biodistribution with active targeting strategies.

Genetic control over biogenic crystal morphogenesis in zebrafish.

Organisms evolve mechanisms that regulate the properties of biogenic crystals to support a wide range of functions, from vision and camouflage to communication and thermal regulation. Yet, the mechanism underlying the formation of diverse intracellular crystals remains enigmatic. Here we unravel the biochemical control over crystal morphogenesis in zebrafish iridophores.

Disease gene prioritization with quantum walks.

Motivation: Disease gene prioritization methods assign scores to genes or proteins according to their likely relevance for a given disease based on a provided set of seed genes. This scoring can be used to find new biologically relevant genes or proteins for many diseases. Although methods based on classical random walks have proven to yield competitive results, quantum walk methods have not been explored to this end.

Mechanical Circulatory Support in Pediatric Myocarditis: Support Strategies and Outcomes in a Nationally Representative Cohort.

Background: Myocarditis is a common cause of pediatric heart failure which may require mechanical circulatory support (MCS). The purpose of this study is to describe MCS strategies used in a nationwide cohort of pediatric patients with myocarditis, identify trends over time, and compare outcomes between MCS strategies.

Methods: This study utilized the Kids' Inpatient Database (KID), a national sample of administrative discharge data.

Organ transformation by environmental disruption of protein integrity and epigenetic memory in Drosophila.

Despite significant progress in understanding epigenetic reprogramming of cells, the mechanistic basis of "organ reprogramming" by (epi-)gene-environment interactions remained largely obscure. Here, we use the ether-induced haltere-to-wing transformations in Drosophila as a model for epigenetic "reprogramming" at the whole organism level. Our findings support a mechanistic chain of events explaining why and how brief embryonic exposure to ether leads to haltere-to-wing transformations manifested at the larval stage and on.

Targeted effect of ischemic preconditioning on the gas exchange threshold in healthy males and females.

Ischemic preconditioning (IPC) appears to improve exercise performance although there is uncertainty about the intensity dependence of this effect. The present study sought to clarify effects of IPC on physiological responses at and below peak oxygen uptake, including the gas exchange threshold (GET). Ten male and female participants completed five cycling ramp tests (10 W/min) to failure, with the final two tests preceded by either IPC (4 × 5 min 220 mmHg bilateral leg occlusions) or SHAM (20 mmHg), in a randomised crossover design.

Carbohydrate dynamics in Populus trees under drought: An expression atlas of genes related to sensing, translocation, and metabolism across organs.

In trees, nonstructural carbohydrates (NSCs) serve as long-term carbon storage and long-distance carbon transport from source to sink. NSC management in response to drought stress is key to our understanding of drought acclimation. However, the molecular mechanisms underlying these processes remain unclear.

Stable Mammalian Serum Albumins Designed for Bacterial Expression.

Albumin is the most abundant protein in the blood serum of mammals and has essential carrier and physiological roles. Albumins are also used in a wide variety of molecular and cellular experiments and in the cultivated meat industry. Despite their importance, however, albumins are challenging for heterologous expression in microbial hosts, likely due to 17 conserved intramolecular disulfide bonds.

Link Prediction with Continuous-Time Classical and Quantum Walks.

Protein-protein interaction (PPI) networks consist of the physical and/or functional interactions between the proteins of an organism, and they form the basis for the field of network medicine. Since the biophysical and high-throughput methods used to form PPI networks are expensive, time-consuming, and often contain inaccuracies, the resulting networks are usually incomplete. In order to infer missing interactions in these networks, we propose a novel class of link prediction methods based on continuous-time classical and quantum walks.

A Combinatorial Library of Lipid Nanoparticles for Cell Type-Specific mRNA Delivery.

Ionizable lipid-based nanoparticles (LNPs) are the most advanced non-viral drug delivery systems for RNA therapeutics and vaccines. However, cell type-specific, extrahepatic mRNA delivery is still a major hurdle, hampering the development of novel therapeutic modalities. Herein, a novel ionizable lipid library is synthesized by modifying hydrophobic tail chains and linkers.

Therapeutic gene silencing of leads to lethality in genetically unstable cancer cells.

The potential of microtubule-associated protein targets for cancer therapeutics remains largely unexplored due to the lack of target-specific agents. Here, we explored the therapeutic potential of targeting cytoskeleton-associated protein 5 (CKAP5), an important microtubule-associated protein, with -targeting siRNAs encapsulated in lipid nanoparticles (LNPs). Our screening of 20 solid cancer cell lines demonstrated selective vulnerability of genetically unstable cancer cell lines in response to silencing.

A Narrative Review of Multiinstitutional Data Registries of Pediatric Congenital Heart Disease in Pediatric Cardiac Anesthesia and Critical Care Medicine.

Congenital heart disease (CHD) is one of the most common birth anomalies. While the care of children with CHD has improved over recent decades, children with CHD who undergo general anesthesia remain at increased risk for morbidity and mortality. Electronic health record systems have enabled institutions to combine data on the management and outcomes of children with CHD in multicenter registries.

Designed High-Redox Potential Laccases Exhibit High Functional Diversity.

White-rot fungi secrete an impressive repertoire of high-redox potential laccases (HRPLs) and peroxidases for efficient oxidation and utilization of lignin. Laccases are attractive enzymes for the chemical industry due to their broad substrate range and low environmental impact. Since expression of functional recombinant HRPLs is challenging, however, iterative-directed evolution protocols have been applied to improve their expression, activity, and stability.

Diagnostic yield and costs associated with a routine pre-operative COVID-19 testing algorithm for asymptomatic patients prior to elective surgery.

Objectives: Infection with COVID-19 presents known and unknown perioperative risks to the patient and operative staff. Pre-operative testing protocols have become widespread, yet little is known about the utility of this practice in asymptomatic patients undergoing elective surgery. We describe the impact and cost of a routine testing protocol on elective surgical procedures in a retrospective series at a single institution.

Exposure Prioritization (): A Screening-Level High-Throughput Chemical Prioritization Tool.

To estimate potential chemical risk, tools are needed to prioritize potential exposures for chemicals with minimal data. Consumer product exposures are a key pathway, and variability in consumer use patterns is an important factor. We designed , a flexible dashboard-type screening-level exposure model, to rapidly visualize exposure rankings from consumer product use.

Supporting the nation's transitioning veterans: Narrative review of practices and recommendations for psychotherapy and counseling of veterans separating from military service.

Each year, approximately 200,000 service members transition out of military service and return to civilian life. For many, the stresses of this military-to-civilian transition are vast and include instabilities in mental health, relationships, employment, education, and housing. Given their unique training, mental health professionals often find themselves on the front lines of efforts to support this population.

Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators.

Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities in the form of biofilms, present a strong challenge to therapeutic treatment due to resistance to conventional antimicrobial therapies. Liposomes can provide a versatile drug-vector strategy for biofilm treatment, but are limited by the need to balance colloidal stability with biofilm penetration. We have discovered a liposomic functionalization strategy, using membrane-embedded moieties of poly[2-(methacryloyloxy)ethyl phosphorylcholine], pMPC, that overcomes this limitation.

Bone strength and composition in spacefaring rodents: systematic review and meta-analysis.

Studying the effects of space travel on bone of experimental animals provides unique advantages, including the ability to perform post-mortem analysis and mechanical testing. To synthesize the available data to assess how much and how consistently bone strength and composition parameters are affected by spaceflight, we systematically identified studies reporting bone health in spacefaring animals from Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. Previously, we reported the effect of spaceflight on bone architecture and turnover in rodents and primates.

Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure.

Hepatokines, secretory proteins from the liver, mediate inter-organ communication to maintain a metabolic balance between food intake and energy expenditure. However, molecular mechanisms by which hepatokine levels are rapidly adjusted following stimuli are largely unknown. Here, we unravel how CNOT6L deadenylase switches off hepatokine expression after responding to stimuli (e.