Kill Two Birds with One Stone: Dual-Metal MOF-Nanozyme-Decorated Hydrogels with ROS-Scavenging, Oxygen-Generating, and Antibacterial Abilities for Accelerating Infected Diabetic Wound Healing.

Diabetic wounds tend to develop into nonhealing wounds associated with the complex inflammatory microenvironment of uncontrollable bacterial infection, reactive oxygen species (ROS) accumulation, and chronic hypoxia. Damaged blood vessels hinder metabolic circulation, aggravating hypoxia, and ROS accumulation and further exacerbating the diabetic wound microenvironment. However, existing treatments with a single functionality have difficulty healing complicated diabetic wounds. Therefore, developing an integrative strategy to improve the hostility of the diabetic wound microenvironment is urgently needed. Herein, multifunctional genipin (GP)-crosslinked chitosan (CS)-based hydrogels decorated with the biomimetic metal-organic framework (MOF)-nanozymes and the natural antibacterial agent chlorogenic acid (CGA), which is named MOF/CGA@GP-CS (MCGC), are prepared. With catalase (CAT)-like activity, these dual-metal MOF-nanozymes are promising bioreactors for simultaneously alleviating ROS accumulation and hypoxia by converting elevated endogenous H2O2 into dissolved oxygen in diabetic wounds. In addition, the other component of natural polyphenolic CGA acts as a mild antibacterial agent, efficiently inhibiting wound infection and avoiding antibiotic resistance. Impressively, the MCGC hydrogels accelerate infected diabetic wound healing by eliminating oxidative stress, increasing oxygenation, and reversing bacterial infection in vivo. In this work, an effective strategy based on multifunctional hydrogel wound dressings is successfully developed and applied in diabetic wound management.

Association of preoperative coronavirus disease 2019 with mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery: An observational cohort study.

STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.

A porphyrin-MOF-based integrated nanozyme system for catalytic cascades and light-enhanced synergistic amplification of cellular oxidative stress.

Peroxidase (POD)-like nanozymes have been found to act as nanoreactors for the generation of reactive oxygen species (ROS) to resolve drug resistance in the tumor microenvironment (TME). Amplifying cellular oxidative stress is considered to be a drug-free strategy to efficiently induce apoptosis in tumor cells. However, the limited content of intracellular hydrogen peroxide (H2O2) extremely restricts the performance of POD-like nanozymes to amplify cellular oxidative stress. Moreover, additional operational processes combined with exogenous reagents to achieve oxidative stress lead to a dilemma of extra cytotoxicity. Here, an integrated iron-porphyrin-MOF-based nanozyme composite named HA@GOx@PCN-224(Fe) (HGPF) was precisely designed and constructed. Generally, the POD-like nanozyme PCN-224(Fe) was used as a platform to immobilize glucose oxidase (GOx), and further embedded with hyaluronic acid (HA) to enable the targeting ability of tumor cells. When endocytosed by tumor cells, intracellular glucose was oxidized to H2O2 and gluconic acid catalyzed by immobilized GOx of HGPF. Afterwards, inspired by heme analogs, H2O2 was catalyzed by iron-porphyrin active sites of the HGPF nanozyme to generate hydroxyl radicals (˙OH). Under light irradiation, the iron-porphyrin of HGPF acted as a photosensitizer to facilely produce singlet oxygen (1O2). Such a synergistic generation of ROS strikingly amplified oxidative stress and induced severe apoptosis in tumor cells. HGPF was expected to integrate intracellular oxygen sources and overcome the dilemma of limited intracellular H2O2 content. Consequently, HGPF was constructed as an integrated nanoreactor to simultaneously achieve light-enhanced catalytic oxidation cascades, providing a promising strategy for a synergistic amplification of cellular oxidative stress.

Novel amphiphilic fluorine-containing nanocarriers for oxygen self-sufficiency "AND" GSH depletion sequentially to enhance photodynamic therapy.

In order to maximize the retention of the photodynamic therapy (PDT) efficacy, while avoiding the dilemma of hypoxia and high reducing substances in tumor tissue, fluoropolymers were synthesized in a simple and effective methods. Fluorous effect with good oxygen carrying capacity was endowed by the fluorine-containing section in fluoropolymers and the perfluorodecalin (PFD) together, the reaction site with GSH was provided by the disulfide bond, which enhanced PDT efficiency through the sequential "AND" logic gate design. Two kind of fluorine-containing nanocarriers (M-Ce6 and E-Ce6) were obtained by solvent evaporation or ultrasound emulsification with PFD, respectively. In vitro, both of them showed promising high ROS generation under photoirradiation. Benefiting by cavitation effects, E-Ce6 had a more significant statistical difference in cellular uptake. Furthermore, the cells incubating with E-Ce6 hardly were noticed that the hypoxia signal appeared under hypoxia, while reducing the intracellular GSH content by more than 15%. Through the sequential "AND" logic gate design, ROS production even under hypoxia and GSH conditions of E-Ce6 was also almost 1.5 times that of Ce6 under normoxia. Enhancing effect of E-Ce6 was 13.47 times and 6.85 times, while selectivity ratio reached 5.13 times and 4.81 times compared with Ce6 and M-Ce6. The two-pronged strategy showed a high potential for delivering the Ce6 to deep inside of cancer cells and killing it in the simulated tumor by PDT. These above results demonstrated the potential of E-Ce6, as oxygen self-sufficiency and GSH depletion nanocarriers for combined enhancement of photodynamic therapy.