RESUMEN
Insufficient drug accumulation in tumors severely limits the antitumor efficiency of hyaluronic acid (HA) nanomedicine in solid tumors due to superficial penetration depth, low cell uptake, and nonspecific drug release. Hence, we constructed a dual NO prodrug (alkynyl-JSK) and doxorubicin prodrug (cis-DOX)-conjugated HA nanoparticle (HA-DOX-JSK NPs), which achieved cascade-boosted drug delivery efficiency based on a relay strategy of NO-mediated deep tumor penetrationâHA target CD44 tumor cell uptakeâtumor microenvironment (TME)-responsive drug release. The nanoparticle demonstrated sustained and locoregionally GSH/GST-triggered NO release and GSH/pH-responsive DOX release in the tumor. The released NO first mediated collagen degradation, causing deep tumor penetration of nanoparticles in the dense extracellular matrix. Immediately, HA was relayed to enhance CD44-targeted tumor cell uptake, and then, the nanoparticles were finally triggered by specific TME to release DOX and NO in the deep tumor. Relying on the relayed delivery strategy, a significant improvement of DOX accumulation in tumors was realized. Moreover, NO depleted GSH-induced intracellular reactive oxygen species, enhancing DOX chemotherapy. Based on this strategy, the tumor inhibition rate in breast cancer was up to 87.8% in vivo. The relay drug-delivery HA system would greatly cascade-boost drug accumulation in deep tumors for efficient solid tumor therapy.
RESUMEN
Bacterial infection-induced excessive inflammation is a major obstacle in diabetic wound healing. Nitric oxide (NO) exhibits significant antibacterial activity but is extremely deficient in diabetes. Hence, a near-infrared (NIR)-triggered NO release system is constructed through codelivery of polyarginine (PArg) and gold nanorods (Au) in an NIR-activatable methylene blue (MB) polypeptide-assembled nanovesicle (Au/PEL-PBA-MB/PArg). Upon NIR irradiation, the quenched MB in the nanovesicles is photoactivated to generate more reactive oxygen species (ROS) to oxidize PArg and release NO in an on-demand controlled manner. With the specific bacterial capture of phenylboronic acid (PBA), NO elevated membrane permeability and boosted bacterial vulnerability in the photothermal therapy (PTT) of the Au nanorods, which is displayed by superior mild PTT antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) at temperatures < 49.7 °C in vitro. Moreover, in vivo, the antibacterial nanovesicles greatly suppressed the burst of MRSA-induced excessive inflammation, NO relayed immunomodulated macrophage polarization from M1 to M2, and the excessive inflammatory phase is successfully transferred to the repair phase. In cooperation with angiogenesis by NO, tissue regeneration is accelerated in MRSA-infected diabetic wounds. Therefore, nanoplatform has considerable potential for accelerating the healing of infected diabetic wounds.
RESUMEN
Since the outbreak of COVID-19, various fields have been damaged to varying degrees, especially in the economic field. According to a comprehensive study of bibliometrics and content analysis, this paper aims at summarizing studies related to the development of the economic field during the COVID-19 epidemic. We search in Web of Science Core Collection using the subjects such as "economics", "economy", "economic", "financial", and then 2274 related documents are collected, which are published from 2020 to 2022. First, this paper uses the mixed qualitative and quantitative analysis methods to analyze the publication status of the countries, institutions, and authors, respectively, and conducts the document co-citation analysis by CiteSpace software. The results showed that the most popular journal is Sustainability, and the most productive research institutions, countries, and authors are primarily located in North American and European countries. Then, it makes an in-depth study of the cooperative network. With the support of Gephi software, this paper employs the social network analysis method to analyze the situation of the country/region cooperation and institutional cooperation. Finally, the content analysis of the related studies is presented to further explore the current challenges. On this basis, this paper analyzes the economic development in the post-epidemic era and draws some conclusions, which provide some references for scholars interested in this field.
RESUMEN
OBJECTIVE: To investigate the clinicopathologic features and differential diagnoses of non-involuting congenital hemangioma (NICH) in children. METHODS: The clinical, morphologic and immunophenotypic characteristics of 22 cases of NICH were retrospectively analyzed. RESULTS: The mean patients' age at diagnosis was 4.2 years, with a male to female ratio of 1.75:1. The tumors were located in the head and face (5 cases), neck (3 cases), body (6 cases), upper limbs (5 cases), and lower limbs (3 cases). Histologically, the tumor was dominated by rather large lobules of small vessels that were mostly rounded, curved, small and thin-walled, and were lined by endothelial cells surrounded by one or more layers of pericytes. The center of the lobules was occupied by one or more thin or thick walled vessels, which were surrounded by fibrous and fatty tissue, which contained abnormal arterial and venous structures. At the edge of the lobules there were lymphatic vessels. Immunohsitochemical study showed that tumor cells in NICH were positive for CD34 (22/22), CD31 (22/22), SMA (22/22), vimentin (22/22) and Glut1 (0/22). D2-40 expression was located at the edge of the capillary lobules. CONCLUSIONS: NICH is a benign lesion. Clinically and pathologically, it needs to be differentiated from rapidly involuting congenital hemangioma, infantile hemangiomas, tufted angioma, vascular malformation, and others.