Scalable Accelerated Materials Discovery of Sustainable Polysaccharide-Based Hydrogels by Autonomous Experimentation and Collaborative Learning.

While some materials can be discovered and engineered using standalone self-driving workflows, coordinating multiple stakeholders and workflows toward a common goal could advance autonomous experimentation (AE) for accelerated materials discovery (AMD). Here, we describe a scalable AMD paradigm based on AE and "collaborative learning". Collaborative learning using a novel consensus Bayesian optimization (BO) model enabled the rapid discovery of mechanically optimized composite polysaccharide hydrogels.

Gelation during Ring-Opening Reactions of Cellulosics with Cyclic Anhydrides: Phenomena and Mechanisms.

Cellulose esters are used in Food and Drug Administration-approved oral formulations, including in amorphous solid dispersions (ASDs). Some bear substituents with terminal carboxyl moieties (e.g.

ω-Carboxyl terminated cellulose esters are effective crystallization inhibitors for challenging drugs.

Polymeric additives are widely used to delay drug crystallization from supersaturated solutions, which is critical for enhancing oral bioavailability by amorphous solid dispersion (ASD). The efficacy of these polymers relies on their capacity to inhibit nucleation and subsequent crystal growth. Drug nucleation is pivotal to crystallization; therefore, effective polymers are essential for suppressing nucleation from supersaturated solutions.

Integrin beta-like 1 is regulated by DNA methylation and increased in heart failure patients.

Aims: Dynamic alterations in cardiac DNA methylation have been implicated in the development of heart failure (HF) with evidence of ischaemic heart disease (IHD); however, there is limited research into cell specific, DNA methylation sensitive genes that are affected by dysregulated DNA methylation patterns. In this study, we aimed to identify DNA methylation sensitive genes in the ischaemic heart and elucidate their role in cardiac fibrosis.

Methods: A multi-omics integrative analysis was carried out on RNA sequencing and methylation sequencing on HF with IHD (n = 9) versus non-failing (n = 9) left ventricular tissue, which identified Integrin beta-like 1 (ITGBL1) as a gene of interest.

Kinetics of Calcite Nucleation onto Sulfated Chitosan Derivatives and Implications for Water-Polysaccharide Interactions during Crystallization of Sparingly Soluble Salts.

Anionic macromolecules are found at sites of CaCO biomineralization in diverse organisms, but their roles in crystallization are not well-understood. We prepared a series of sulfated chitosan derivatives with varied positions and degrees of sulfation, DS(SO ), and measured calcite nucleation rate onto these materials. Fitting the classical nucleation theory model to the kinetic data reveals the interfacial free energy of the calcite-polysaccharide-solution system, γ, is lowest for nonsulfated controls and increases with DS(SO ).

6-Carboxycellulose Acetate Butyrate: Effectiveness as an Amorphous Solid Dispersion Polymer.

Amorphous solid dispersion (ASD) in a polymer matrix is a powerful method for enhancing the solubility and bioavailability of otherwise crystalline, poorly water-soluble drugs. 6-Carboxycellulose acetate butyrate (CCAB) is a relatively new commercial cellulose derivative that was introduced for use in waterborne coating applications. As CCAB is an amphiphilic, carboxyl-containing, high glass transition temperature () polymer, characteristics essential to excellent ASD polymer performance, we chose to explore its ASD potential.

Selective cross-metathesis of cellobiose derivatives with amido-functionalized olefinic structures: A model study for synthesis of cellulosic diblock copolymers.

This work describes a model study for synthesis of cellulose-based block copolymers, investigating selective coupling of peracetyl β-d-cellobiose and perethyl β-d-cellobiose at their reducing-ends by olefin cross-metathesis (CM). Herein we explore suitable pairs of ω-alkenamides that permit selective, quantitative coupling by CM. Condensation reactions of hepta-O-acetyl-β-d-cellobiosylamine or hepta-O-ethyl-β-d-cellobiosylamine with acyl chlorides afforded the corresponding N-(β-d-cellobiosyl)-ω-alkenamide derivatives with an aromatic olefin or linear olefinic structures.

Synthesis and real-time characterization of self-healing, injectable, fast-gelling hydrogels based on alginate multi-reducing end polysaccharides (MREPs).

Polysaccharide-based hydrogels are promising for many biomedical applications including drug delivery, wound healing, and tissue engineering. We illustrate herein self-healing, injectable, fast-gelling hydrogels prepared from multi-reducing end polysaccharides, recently introduced by the Edgar group. Simple condensation of reducing ends from multi-reducing end alginate (M-Alg) with amines from polyethylene imine (PEI) in water affords a dynamic, hydrophilic polysaccharide network.

Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset.

Dextran Macroinitiator for Synthesis of Polysaccharide--Polypeptide Block Copolymers via NCA Ring-Opening Polymerization.

Synthesis of polysaccharide--polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in -carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran--polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis.

All-polysaccharide, self-healing, pH-sensitive, in situ-forming hydrogel of carboxymethyl chitosan and aldehyde-functionalized hydroxyethyl cellulose.

In situ forming hydrogels are promising for biomedical applications, especially in drug delivery. The precursor solution can be injected at the target site, where it undergoes a sol-gel transition to afford a hydrogel. In this sense, the most significant characteristic of these hydrogels is fast gelation behavior after injection.

Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.

Polysaccharide Aldehydes and Ketones: Synthesis and Reactivity.

Polysaccharides are biodegradable, abundant, sustainable, and often benign natural polymers. The achievement of selective modification of polysaccharides is important for targeting specific properties and structures and will benefit future development of highly functional, sustainable materials. The synthesis of polysaccharides containing aldehyde or ketone moieties is a promising tool for achieving this goal because of the rich chemistry of aldehyde or ketone groups, including Schiff base formation, nucleophilic addition, and reductive amination.

Regioselective and controlled-density branching in amylose esters.

Herein, we report creation of methodology for one-pot synthesis of 2,3-O-acetyl-6-bromo-6-deoxy (2,3Ac-6Br) amylose with controlled degree of substitution of bromide (DS(Br)) followed by quantitative azide substitution as a route to branched polysaccharide derivatives. This methodology affords complete control of "tine" location, and strong control of degree of branching of comb-structured polymers. In this way, we achieved bromination strictly at C6 and esterification at the other hydroxy groups, where the DS(Br) at C6 was well-controlled by bromination/acylation conditions in the one-pot process.

Dose-dependent changes in cardiac function, strain and remodelling in a preclinical model of heart base irradiation.

Background And Purpose: Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation.

Dess-Martin oxidation of hydroxypropyl and hydroxyethyl cellulose, and exploration of their polysaccharide/polypeptide hydrogels.

Oxidation of polysaccharides can provide biomaterials with aldehyde and ketone functional groups, which are particularly useful in biomedical applications, like drug delivery, tissue adhesion and hydrogel preparation. However, despite their potential, only a few such methods have been reported, and achieving selective, quantitative oxidation of polysaccharides remains challenging. Herein we report utilization of a mild oxidant, Dess-Martin periodinane, for the chemoselective oxidation of hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC).

Reductive amination of oxidized hydroxypropyl cellulose with ω-aminoalkanoic acids as an efficient route to zwitterionic derivatives.

Zwitterionic polymers, with their equal amounts of cationic and anionic functional groups, have found widespread utility including as non-fouling coatings, hydrogel materials, stabilizers, antifreeze materials, and drug carriers. Polysaccharide-derived zwitterionic polymers are attractive because of their sustainable origin, potential for lower toxicity, and possible biodegradability, but previous methods for synthesis of zwitterionic polysaccharide derivatives have been limited in terms of flexibility and attainable degree of substitution (DS) of charged entities. We report herein successful design and synthesis of zwitterionic polysaccharide derivatives, in this case based on cellulose, by reductive amination of oxidized 2-hydroxypropyl cellulose (Ox-HPC) with ω-aminoalkanoic acids.

BH4 supplementation reduces retinal cell death in ischaemic retinopathy.

Dysregulation of nitric oxide (NO) production can cause ischaemic retinal injury and result in blindness. How this dysregulation occurs is poorly understood but thought to be due to an impairment in NO synthase function (NOS) and nitro-oxidative stress. Here we investigated the possibility of correcting this defective NOS activity by supplementation with the cofactor tetrahydrobiopterin, BH.

Smart fluorescent polysaccharides: Recent developments and applications.

Polysaccharides are ubiquitous, generally benign in nature, and compatible with many tissues in biomedical situations, making them appealing candidates for new materials such as therapeutic agents and sensors. Fluorescent labeling can create the ability to sensitively monitor distribution and transport of polysaccharide-based materials, which can for example further illuminate drug-delivery mechanisms and therefore improve design of delivery systems. Herein, we review fluorophore selection and ways of appending polysaccharides, utility of the product fluorescent polysaccharides as new smart materials, and their stimulus-responsive nature, with focus on their biomedical applications as environment-sensitive biosensors, imaging, and as molecular rulers.

A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity.

Purpose: Despite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation.

PLAC8-Mediated Activation of NOX4 Signalling Restores Angiogenic Function of Endothelial Colony-Forming Cells in Experimental Hypoxia.

Ischaemic cardiovascular disease is associated with tissue hypoxia as a significant determinant of angiogenic dysfunction and adverse remodelling. While cord blood-derived endothelial colony-forming cells (CB-ECFCs) hold clear therapeutic potential due to their enhanced angiogenic and proliferative capacity, their impaired functionality within the disease microenvironment represents a major barrier to clinical translation. The aim of this study was to define the specific contribution of NOX4 NADPH oxidase, which we previously reported as a key CB-ECFC regulator, to hypoxia-induced dysfunction and its potential as a therapeutic target.

Synthesis and Characterization of Multi-Reducing-End Polysaccharides.

Site-specific modification is a great challenge for polysaccharide scientists. Chemo- and regioselective modification of polysaccharide chains can provide many useful natural-based materials and help us illuminate fundamental structure-property relationships of polysaccharide derivatives. The hemiacetal reducing end of a polysaccharide is in equilibrium with its ring-opened aldehyde form, making it the most uniquely reactive site on the polysaccharide molecule, ideal for regioselective decoration such as imine formation.

Chitosan as a Canvas for Studies of Macromolecular Controls on CaCO Biological Crystallization.

A mechanistic understanding of how macromolecules, typically as an organic matrix, nucleate and grow crystals to produce functional biomineral structures remains elusive. Advances in structural biology indicate that polysaccharides (e.g.

Oxidized hydroxypropyl cellulose/carboxymethyl chitosan hydrogels permit pH-responsive, targeted drug release.

Polysaccharide-based Schiff base hydrogels have promise for drug delivery, tissue engineering, and many other applications due to their reversible imine bond crosslinks. We describe herein pH-responsive, injectable, and self-healing hydrogels prepared by reacting oxidized hydroxypropyl cellulose (Ox-HPC) with carboxymethyl chitosan (CMCS). Simple combination of ketones from Ox-HPC side chains with amines from CMCS in water provides a dynamic, hydrophilic polysaccharide network.