Hypoxia mitigation by manganese-doped carbon dots for synergistic photodynamic therapy of oral squamous cell carcinoma

Photodynamic therapy (PDT) is widely used for cancer treatment due to its non-invasive and precise effectiveness, however, hypoxia in the tumor microenvironment greatly limits the efficacy of photodynamic therapy. Compared with conventional photosensitizers, carbon dots (CDs) have great potential. Therefore, developing a water-soluble, low-toxicity photosensitizer based on CDs is particularly important, especially one that can enhance the photodynamic efficacy using the tumor microenvironment to produce oxygen. Herein, manganese-doped carbon dot (Mn-CDs, ∼2.7 nm) nanoenzymes with excellent biocompatibility were prepared by a solvothermal method using ethylenediaminetetraacetic acid manganese disodium salt hydrate and o-phenylenediamine as precursors. TEM, AFM, HR-TEM, XRD, XPS, FT-IR, ζ potential, DLS, UV-Vis, and PL spectra were used to characterize the Mn-CDs. Cancer resistance was assessed using the CCK-8 kit, calcein AM versus propidium iodide (PI) kit, and the Annexin V-FITC/PI cell apoptosis assay kit. The obtained Mn-CDs have excellent near-infrared emission properties, stability, and efficient 1O2 generation. Notably, the manganese doping renders CDs with catalase (CAT)-like activity, which leads to the decomposition of acidic H2O2in situ to generate O2, enhancing the PDT efficacy against OSCC-9 cells under 635 nm (300 mW·cm−2) irradiation. Thus, this work provides a simple and feasible method for the development of water-soluble photosensitizers with oxygen production, presenting good biosafety for PDT in hypoxic tumors

Survey of Research on Personalized News Recommendation Approaches

Personalized news recommendation is an important technology to help users obtain the news information they are interested in and alleviate information overload. In recent years, with the development of information technology and society, personalized news recommendation has been increasingly widely studied, and has achieved remarkable success in improving the news reading experience of users. This paper aims to systematically summarize personalized news recommendation methods based on deep learning. Firstly, it introduces personalized news recommendation methods and analyzes their characteristics and influencing factors. Then, the overall framework of personalized news recommendation is given, and the personalized news recommendation methods based on deep learning are analyzed and summarized. On this basis, it focuses on personalized news recommendation methods based on graph structure learning, including user-news interaction graph, knowledge graph and social relationship graph. Finally, it analyzes the challenges of the current personalized news recommendation, discusses how to solve the problems of data sparsity, model interpretability, diversity of recommendation results and news privacy protection in personalized news recommendation system, and puts forward more specific and operable research ideas in the future research direction

Blood glucose level affects prognosis of patients who received intravenous thrombolysis after acute ischemic stroke? A meta-analysis

Background and objectivesIntravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for the occurrence, development, and prognosis of ischemic stroke. This meta-analysis purposefully estimates the association between hyperglycemia and poor prognosis in acute ischemic stroke patients receiving intravenous rtPA thrombolytic therapy.Materials and methodsAccording to the predefined inclusion criteria, we searched PubMed, Web of Science, and Cochrane Library databases. The association of high blood glucose(>140mg/dl) with symptomatic intracranial hemorrhage (sICH), poor clinical outcome and mortality at 90 days post-rtPA thrombolysis was studied using both a common effects model and a random effects model. Odds ratios (ORs) were plotted on forest plots.ResultsOf a total cohort of 2565 patients who received intravenous thrombolytic therapy, 721 had higher blood glucose. High glucose level significantly increased the odds of sICH (OR 1.80; 95% confidence interval(95%CI): 1.30- 2.50) and poor clinical outcome at 90 days (OR 1.82; 95%CI: 1.52-2.19), and all-cause mortality at 90 days (OR 2.51; 95%CI:1.65-3.82).ConclusionsIn our meta-analysis, high blood glucose was significantly associated with sICH, poor clinical outcome and higher mortality at 90 days

SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Abstract Background Doxorubicin is the preferred chemotherapeuticdrug for osteosarcoma treatment of which clinical efficacy is limited because of its chemo-resistance and cardiac toxicity. It is necessary to develop the combination regimen with complementary molecular mechanisms to reduce the side effects and enhance sensitivity of Doxorubicin. EGCG is a polyphenol in green tea with antitumor bioactivity,which has been found that its combination with certain chemotherapeutic drugs could improve the antitumor efficiency. Methods In this study, MTT assay was used to detect the cell growth inhibition The CD133+/CD44+ cells were isolated from U2OS and SaoS2 cell lines using magnetic-activated cell sorting and identified by flow cytometry analysis. qRT-PCR was used for determining the relative mRNA levels of key genes. Immunofluorescence was performed to evaluate the autophagy flux alterations. Self-renewal ability was accessed by sphere-forming assay. Tumorigenicity in nude mice was preformed to evaluate tumorigenicity in vivo. Results We found that EGCG targeting LncRNA SOX2OT variant 7 produced synergistic effects with Doxorubicin on osteosarcoma cell growth inhibition. On the one hand, EGCG could reduce the Doxorubicin-induced pro-survival autophagy through decreasing SOX2OT variant 7 to improve the growth inhibition of Doxorubicin. On the other hand, EGCG could partially inactivate Notch3/DLL3 signaling cascade targeting SOX2OT variant 7 to reduce the stemness then abated drug-resistance of osteosarcoma cells. Conclusions This study will help to reveal the molecular mechanisms of synergistic effects of EGCG and Doxorubicin on OS chemotherapy and improve the clinical efficacy of chemotherapy as well as provide a basis for developing antitumor drugs targeting osteosarcoma stem cells