Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients’ clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464–0.9778), 0.9760 (0.9613–0.9906), and 0.9246 (0.8763–0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.

Reactive oxygen species (ROS) are the weapons of neutrophiles against bacterial pathogens, and also the central effectors in reactive oxygen therapy for skin and soft tissue infection. Nanozymes that spontaneously generate ROS under physiological conditions are new antibacterials that hold promise towards multidrug resistant pathogens. The clinical use of the nanozymes is however limited by their low biocompatibility and toxicity in vivo. Here, we develop an oleic acid (OA) nanoemulsion template method for the one-pot synthesis of OA-manganese dioxide (MnO₂) nanozyme. The OA-MnO₂ nanozyme showed high stability and biocompatibility under physiological conditions with marked oxidase-like activity. The ROS generated by the OA-MnO₂ nanozyme effectively kill the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli strains. Moreover, the OA-MnO₂ nanozyme shows promising abilities to prevent and destruct biofilm formation by Staphylococcus aureus, and result in superior in vivo antibacterial performance as compared to vancomycin. The reactive oxygen therapy based on OA-MnO₂ nanozyme cures the infected skin and promotes wound healing in mice, manifesting its potential use in skin and soft tissue infection.

Staphylococcus aureus (S. aureus) related staphylococcal infection is one of the most common types of hospital-acquired infections, which requires selective and effective treatment in clinical practice. Considering gelatinase as a characteristic feature of S. aureus, gelatinase-responsive release of the antibiotic reagent thereby can target the pathogenic S. aureus while sparing beneficial bacteria in the microflora. In this work, we design a hybrid antibacterial photodynamic peptide (APP, Ce6-GKRWWKWWRRPLGVRGC) based on the polycationic antimicrobial peptide GKRWWKWWRR by introducing a photosensitizer chlorin e6 (Ce6) at the N-terminus, a cysteine residue at the C-terminus, and a gelatinase cleavage site (PLGVRG) inserted between the C-terminal cysteine and the polycationic peptide. This multi-motif peptide assembles with gold nanoclusters (AuNc) via Au–thiol bonding and affords a gelatinase-responsive antibacterial photodynamic nanocomposite (GRAPN). In vitro results show that the gelatinase secreted by S. aureus can cleave and release APP from AuNc, thereby resulting in preferential killing of S. aureus over E. coli. In a mouse model of staphylococcal skin wound infection, by integrating gelatinase-responsive drug release and the synergistic effect of a photodynamic agent and APP, GRAPN exhibits a marked photodynamic antibacterial activity, effectively eradicates S. aureus infection, and promotes rapid healing of the infected wounds.

Bacterial infection of wounds delays the healing process, increases the risk of chronic trauma associated with pain and complications, and offers a breeding ground for drug-resistant bacteria. A rapid and effective eradication of the bacterial species in the wound area is thus important. Herein, we designed a phototherapeutic antibacterial platform based on peptides and copper sulfide nanodots (CuS NDs) for multi-mechanistic eradication of bacteria colonized on the wound surface. The antimicrobial peptide weaves into a network in the form of a hydrogel, which supports CuS NDs to generate heat and produce reactive oxygen species (ROS) under the irradiation of near-infrared light (NIR). The heat and ROS generated in situ act as non-contact-based antibacterial factors and together with contact-based antimicrobial peptides cause irreversible membrane destruction, cell content damage, and thermal ablation of the bacteria. Lastly, nanodot-doped peptide hydrogels combined with collagen showed complete bacterial elimination and significantly accelerated wound healing in a splint-fixed mouse infection model.

The incidence of intrauterine adhesions (IUA) has increased with the rising utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing IUAs, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid (NCHA) gel. According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium and reducing the abnormal deposition of fibrin, thus preventing IUA more effectively. This study provides a promising strategy for treating and preventing IUA.