Multifunctional Oxidized Dextran-Metformin as a Tissue-Adhesive Hydrogel to Prevent Postoperative Peritoneal Adhesions in Patients with Metabolic Syndrome.

Patients with metabolic syndrome (MetS) undergoing surgery are at high risk of developing peritoneal adhesions and other severe postoperative complications. However, the single shielding function and absence of physiological activity render conventional methods less useful in preventing adhesions in patients with MetS. To address this challenge, a convenient method is introduced for developing a novel tissue-adhesive hydrogel called oxidized dextran-metformin (ODE-ME) via Schiff base linkages. This injectable ODE-ME hydrogel exhibits excellent tissue-adhesive properties and various physiological functions, particularly enhanced antibacterial effects. Furthermore, in vivo experiments demonstrate that the hydrogel can effectively alleviate hyperglycemia, reduce excessive inflammation, and improve fibrinolytic activity in MetS mice, thereby preventing adhesions and promoting incisional healing. The hydrogel concurrently isolates injured tissues and lowers the blood glucose levels immediately after surgery in mice. Therefore, the ODE-ME hydrogel functions as a multifunctional barrier material and has potential for preventing postoperative peritoneal adhesions in patients with MetS in clinical settings.

Chromium-Mediated and Ligand-Dependent Activity Engineering of Boron-Doped g-C3N4 Photo-oxidative Nanozymes for Breaking the pH Limitation.

How to overcome the intrinsic low activity of most oxidase and peroxidase mimics at neutral pH has been extremely challenging. Herein, we represent a chromium-mediated and ligand-dependent strategy to activate the oxidase-like activity of boron-doped g-C3N4 (B-g-C3N4, denoted as BG), aiming at breaking the pH limitation. Cr (III) can be in situ oxidized to Cr (IV) by generated •O2- upon UV light irradiation, which then works as a catalysis mediator to oxidize TMB under a neutral environment. Excitingly, the TMB oxidation can be rationally modulated by ligands on the BG coordinating with chromium. We verify that the PEI-Cr3+ coordination outperformed Cit-PEI-Cr3+ on the oxidase-like activity through a more accelerated electron transfer, unveiled by the Gauss theoretical calculations. This study highlights a paradigm of tuning the coordination environment on nanozyme surface via the ligand engineering strategy for boosting the oxidase-mimicking activity and breaking the pH limitation. Meanwhile, the catalysis-based colorimetric assay for accurate and selective identification of Cr3+ was achieved.

One-Step Construction of Tryptophan-Derived Small Molecule Hydrogels for Antibacterial Materials.

Amino acid-based hydrogels have received widespread attention because of their wide range of sources, biodegradability, and biocompatibility. Despite considerable progress, the development of such hydrogels has been limited by critical problems such as bacterial infection and complex preparation. Herein, by using the non-toxic gluconolactone (GDL) to adjust the pH of the solution to induce the rapid self-assembly of N-[(benzyloxy)carbonyl]-L-tryptophan (ZW) to form a three-dimensional (3D) gel network, we developed a stable and effective self-assembled small-molecule hydrogel. Characterization assays and molecular dynamics studies indicate that π-π stacking and hydrogen bonding are the main drivers of self-assembly between ZW molecules. In vitro experiments further confirmed this material's sustained release properties, low cytotoxicity, and excellent antibacterial activity, particularly against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. This study provides a different and innovative perspective for the further development of antibacterial materials based on amino acid derivatives.

Self-assembly hydrogels of therapeutic agents for local drug delivery.

Advanced drug delivery systems are of vital importance to enhance therapeutic efficacy. Among various recently developed formulations, self-assembling hydrogels composed of therapeutic agents have shown promising potential for local drug delivery owing to their excellent biocompatibility, high drug-loading efficiency, low systemic toxicity, and sustained drug release behavior. In particular, therapeutic agents self-assembling hydrogels with well-defined nanostructures are beneficial for direct delivery to the target site via injection, not only improving drug availability, but also extending their retention time and promoting cellular uptake. In brief, the self-assembly approach offers better opportunities to improve the precision of pharmaceutical treatment and achieve superior treatment efficacies. In this review, we intend to cover the recent developments in therapeutic agent self-assembling hydrogels. First, the molecular structures, self-assembly mechanisms, and application of self-assembling hydrogels are systematically outlined. Then, we summarize the various self-assembly strategies, including the single therapeutic agent, metal-coordination, enzyme-instruction, and co-assembly of multiple therapeutic agents. Finally, the potential challenges and future perspectives are discussed. We hope that this review will provide useful insights into the design and preparation of therapeutic agent self-assembling hydrogels.

Molecular Dynamics-Assisted Design of High Temperature-Resistant Polyacrylamide/Poloxamer Interpenetrating Network Hydrogels.

Polyacrylamide has promising applications in a wide variety of fields. However, conventional polyacrylamide is prone to hydrolysis and thermal degradation under high temperature conditions, resulting in a decrease in solution viscosity with increasing temperature, which limits its practical effect. Herein, combining molecular dynamics and practical experiments, we explored a facile and fast mixing strategy to enhance the thermal stability of polyacrylamide by adding common poloxamers to form the interpenetrating network hydrogel. The blending model of three synthetic polyacrylamides (cationic, anionic, and nonionic) and poloxamers was first established, and then the interaction process between them was simulated by all-atom molecular dynamics. In the results, it was found that the hydrogen bonding between the amide groups on all polymers and the oxygen-containing groups (ether and hydroxyl groups) on poloxamers is very strong, which may be the key to improve the high temperature resistance of the hydrogel. Subsequent rheological tests also showed that poloxamers can indeed significantly improve the stability and viscosity of nonionic polyacrylamide containing only amide groups at high temperatures and can maintain a high viscosity of 3550 mPa·S at 80 °C. Transmission electron microscopy further showed that the nonionic polyacrylamide/poloxamer mixture further formed an interpenetrating network structure. In addition, the Fourier transform infrared test also proved the existence of strong hydrogen bonding between the two polymers. This work provides a useful idea for improving the properties of polyacrylamide, especially for the design of high temperature materials for physical blending.

Self-healing, injectable hydrogel based on dual dynamic covalent cross-linking against postoperative abdominal cavity adhesion.

Clinically, increasing the peritoneal barrier is an effective adjunct to reducing postoperative peritoneal adhesion. This study presents a facile template for preparing a supramolecular hybrid hydrogel through dynamic covalent cross-linking between carboxymethyl chitosan (CMCS), 2-formylphenylboronic acid (2-FPBA), and quercetin (Que). The as-prepared complex CMCS/2-FPBA/Que (CFQ) hydrogel exhibited favorable antibacterial, anti-inflammatory, and antioxidant effects. A L929 cytotoxicity evaluation confirmed the favorable cytocompatibility of the CFQ hydrogel. The postoperative anti-adhesion ability of the CFQ hydrogel was further evaluated in rats with lateral wall defects and cecal abrasions. Compared with control groups, the tissue adhesion rate was significantly reduced by increasing the Que concentration in all the hydrogel-treated groups. Additionally, the sustained-release time of the C3F0.8Q0.08 hydrogel can exceed 14 days, which is highly desirable for clinical wound treatment. STATEMENT OF SIGNIFICANCE: Postoperative adhesions are a very common postoperative complication that seriously affects the quality of life of patients. The currently commonly used methods for preventing adhesion mainly use degradable barrier materials for physical separation. In this study, we prepared a dual dynamic covalently cross-linked CFQ hydrogel, which is not only degradable and injectable, but also has multiple properties such as antibacterial, antioxidant and anti-inflammatory, which can effectively prevent postoperative adhesion and promote wound healing.

Theory-Guided Regulation of FeN4 Spin State by Neighboring Cu Atoms for Enhanced Oxygen Reduction Electrocatalysis in Flexible Metal-Air Batteries.

Iron, nitrogen-codoped carbon (Fe-N-C) nanocomposites have emerged as viable electrocatalysts for the oxygen reduction reaction (ORR) due to the formation of FeNx Cy coordination moieties. In this study, results from first-principles calculations show a nearly linear correlation of the energy barriers of key reaction steps with the Fe magnetic moment. Experimentally, when single Cu sites are incorporated into Fe-N-C aerogels (denoted as NCAG/Fe-Cu), the Fe centers exhibit a reduced magnetic moment and markedly enhanced ORR activity within a wide pH range of 0-14. With the NCAG/Fe-Cu nanocomposites used as the cathode catalyst in a neutral/quasi-solid aluminum-air and alkaline/quasi-solid zinc-air battery, both achieve a remarkable performance with an ultrahigh open-circuit voltage of 2.00 and 1.51 V, large power density of 130 and 186 mW cm-2 , and good mechanical flexibility, all markedly better than those with commercial Pt/C or Pt/C-RuO2 catalysts at the cathode.

Potential metal-related strategies for prevention and treatment of COVID-19.

Abstract: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19.

Facile Preparation of Drug-Releasing Supramolecular Hydrogel for Preventing Postoperative Peritoneal Adhesion.

Hydrogels have attracted widespread attention for breaking the bottlenecks faced during facile drug delivery. To date, the preparation of jelly carriers for hydrophobic drugs remains challenging. In this study, by evaporating ethanol to drive the formation of hydrogen bonds, hydrophilic poly(vinyl alcohol) (PVA) and certain hydrophobic compounds [luteolin (LUT), quercetin (QUE), and myricetin (MYR)] were rapidly prepared into supramolecular hydrogel within 10 min. The gelation performance of these three hydrogels changed regularly with the changing sequence of LUT, QUE, and MYR. An investigation of the gelation pathway of these hybrid gels reveals that the formation of this type of gel follows a simple supramolecular self-assembly process, called "hydrophobe-hydrophile crosslinked gelation". Because the hydrogen bond between PVA and the drug is noncovalent and reversible, the hydrogel has good plasticity and self-healing properties, while the drugs can be controllably released by tuning the output stimuli. Using a rat sidewall-cecum abrasion adhesion model, the as-prepared hydrogel was highly efficient and safe in preventing postsurgical adhesion. This work provides a useful archetypical template for researchers interested in the efficient delivery and controllable release of hydrophobic drugs.

A natural cordycepin/chitosan complex hydrogel with outstanding self-healable and wound healing properties.

The chitosan-based hydrogel dressings have been intensively engaged in wound healing. In respect to the relatively unsatisfied anti-bacterial performance of chitosan, we developed a self-healable cordycepin (abbreviated to CY)/chitosan (abbreviated to CS) hydrogel dressing cross linking by non-covalent bonds (hydrogen bond and electrostatic interaction) for wound healing through one-step 'freeze-thaw' method without adding any cross-linking agent. The as-prepared hybrid hydrogel exhibited excellent biocompatibility, suitable swelling ratio and desired mechanical strength, providing remarkable antimicrobial effect with no side effects in vitro. The self-healable property enables this hydrogel to adapt irregularly shaped wound defects without premolding. Moreover, our in vivo experiments confirmed that CY/CS hydrogel served as a quicker re-epithelization of skin wounds and an apparent increasing collagen deposition compared with chitosan hydrogels. Additionally, the CY/CS hydrogel significantly increased the expressions of epithelial regeneration markers including laminin and involucrin. The present study highlights a facile hydrogel strategy to balance and optimize the biocompatibility, swelling ratio and self-adapting ability for treating wound healing.

Gambling, Delay, and Probability Discounting in Adults With and Without ADHD.

OBJECTIVE: We investigated the relationship between impulsivity, as measured by delay and probability discounting, and gambling-related cognitions and behavior in adults with and without ADHD. METHOD: Adults who met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnostic criteria for ADHD (n = 31) and controls (n = 29) were recruited from the community. All completed an interview that included an assessment of psychiatric disorders, gambling questionnaires, and simulated gambling, delay, and probability discounting tasks. RESULTS: The ADHD group was more likely to meet the criteria for problem gambling and was more impulsive than controls based on a composite discounting measure. ADHD symptoms were correlated with gambling-related cognitions and behavior. Probability, but not delay discounting, explained significant variance in gambling-related measures after controlling for ADHD symptoms. DISCUSSION: Results confirm an association between adult ADHD and gambling, and suggest that the facets of impulsivity related to risk proneness may be an independent risk factor for problem gambling in this population.