Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells. A single-dose injection of MRD hydrogel retarded the growth of primary melanoma tumors by more than 95% due to loaded melittin and DOX, with concomitant recruitment of activated natural killer cells in the tumors. Furthermore, MRD hydrogel can activate dendritic cells of draining lymph nodes, specifically deplete M2-like tumor-associated macrophages (TAMs), and produce active, cytotoxic T cells to further defend the cells against remaining tumors, providing potent anticancer efficacy against subcutaneous and metastatic tumors in vivo. Multidose injection of MRD hydrogel eliminated 50% of the primary tumors and provided a strong immunological memory effect against tumor rechallenge after eradication of the initial tumors. Owing to its abilities to perform controlled drug release, regulate innate immune cells, deplete M2-like TAMs, direct anticancer and immune-stimulating capabilities, and reshape immunosuppressive TMEs, MRD hydrogel may serve as a powerful tool for anticancer applications.

IMPORTANCE Ocular manifestations and outcomes in children with confirmed coronavirus disease 2019 , relevant affecting factors, and differences in ocular disease between children and adults have yet to be fully understood. OBJECTIVE To investigate ocular manifestations and clinical characteristics of children with laboratory-confirmed COVID-19. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study was conducted at Wuhan Children's Hospital in Wuhan, China. Children with COVID-19 confirmed by severe acute respiratory syndrome coronavirus disease 2 nucleic acid tests of upper respiratory tract specimens between January 26 and March 18, 2020, were included. MAIN OUTCOMES AND MEASURES Onset clinical symptoms and duration, ocular symptoms, and needs for medication. RESULTS A total of 216 pediatric patients were included, among whom 134 (62%) were boys, with a median (interquartile range) age of 7.25 (2.6-11.6) years. Based on the exposure history, 193 children (89.4%) had a confirmed (173 [80.1%]) or suspected (20 [9.3%]) family member with COVID-19 infection. The most common symptoms among symptomatic children were fever (81 [37.5%]) and cough (79 [36.6%]). Of 216 children, 93 (43.1%) had no systemic or respiratory symptoms. All children with mild (101 [46.8%]) or moderate (115 [53.2%]) symptoms recovered without reported death. Forty-nine children (22.7%) showed various ocular manifestations, of which 9 had ocular complaints being the initial manifestations of COVID-19. The common ocular manifestations were conjunctival discharge (27 [55.1%]), eye rubbing (19 [38.8%]), and conjunctival congestion (5 [10.2%]). Children with systemic symptoms (29.3% vs 14.0%; difference, 15.3%; 95% CI, 9.8%-20.7%; P = .008) or with cough (31.6% vs 17.5%; difference, 14.1%; 95% CI, 8.0%-20.3%; P = .02) were more likely to develop ocular symptoms. Ocular symptoms were typically mild, and children recovered or improved. CONCLUSIONS AND RELEVANCEIn this cross-sectional study, children hospitalized with COVID-19 in Wuhan, China, presented with a series of onset symptoms including fever, cough, and ocular manifestations, such as conjunctival discharge, eye rubbing, and conjunctival congestion. Patients' systemic clinical symptoms or cough were associated with ocular symptoms. Ocular symptoms recovered or improved eventually.

A biocompatible hydrogel self-assembled from a peptide comprised of a peptide backbone containing Arg-Gly-Asp (RGD) sequence and a hydrophobic N-fluorenyl-9-methoxycarbonyl (FMOC) tail was designed and prepared to load antiproliferative model drug (5-fluorouracil, 5-Fu). After administering this 5-Fu-loaded peptide hydrogel in the filtering surgery of rabbit eyes, because of the sustained release of 5-Fu from the hydrogel to inhibit the scleral flap fibrosis efficiently, the pathology and immunohistochemistry demonstrate that the filtration fistula is patent without postoperative scarring formation, resulting in the significantly low intraocular pressure (IOP) of the rabbit eyes within postoperative 28 days. In a comparison with the conventional 5-Fu exposure, the strategy demonstrated here presents several advantages including providing convenience and preventing the toxicity of 5-Fu to the surrounding ocular tissues efficiently, suggesting a feasibility of this peptide hydrogel as a potential implanted drug delivery system for the inhibition of postoperative scarring formation.