IGF2BP3 suppresses ferroptosis in lung adenocarcinoma by m6A-dependent regulation of TFAP2A to transcriptionally activate SLC7A11/GPX4.

Ferroptosis is recently discovered as an important player in the initiation, proliferation, and progression of human tumors. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported as an oncogene in multiple types of cancers, including lung adenocarcinoma (LUAD). However, little research has been designed to investigate the regulation of IGF2BP3 on ferroptosis in LUAD. qRT-PCR and western blot were used to measure the mRNA and protein expression of IGF2BP3 and transcription factor AP-2 alpha (TFAP2A). CCK-8 assay was performed to determine cell viability. DCFH-DA and C11-BODIPY staining were used to detect the levels of intracellular reactive oxygen species (ROS) and lipid ROS. The corresponding assay kits were used to analyze the levels of malondialdehyde (MDA) and glutathione (GSH). SRAMP website and m6A RNA immunoprecipitation (Me-RIP) were used to predict and confirm the m6A modification of TFAP2A. RIP experiments were conducted to confirm the binding of IGF2BP3 and TFAP2A. RNA stability assay was performed using actinomycin D. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter experiments were performed to confirm the interaction between TFAP2A and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4). Mice xenotransplant model was also constructed to explore the effect of IGF2BP3 on LUAD tumor growth and ferroptosis. IGF2BP3 and TFAP2A were both highly expressed in LUAD. IGF2BP3 or TFAP2A knockdown induced ferroptosis by aggravating erastin-induced cell viability suppression, increasing the production of intracellular ROS, lipid ROS, and MDA, and decreasing GSH synthesis, GSH/GSSG ratio, and cystine uptake. Mechanistically, IGF2BP3 stabilized TFAP2A expression via m6A modification. Moreover, sh-IGF2BP3-mediated ferroptosis was significantly abated by TFAP2A overexpression. Furthermore, TFAP2A binds to the promoters of SLC7A11 and GPX4 to promote their transcription. Also, IGF2BP3 depletion suppressed LUAD tumor growth by inducing ferroptosis in mice. IGF2BP3 suppresses ferroptosis in LUAD by m6A-dependent regulation of TFAP2A to promote the transcription of SLC7A11 and GPX4. Our findings suggest that targeting IGF2BP3/TFAP2A/SLC7A11/GPX4 axis might be a potential therapeutic choice to increase ferroptosis sensitivity in LUAD.

Polyethylene glycol-modified nanoscale conjugated polymer for the photothermal therapy of lung cancer.

Killing tumor cells efficiently with photothermal therapy remains a huge challenge. In this study, we successfully prepared a novel polymer with photothermal conversion capability via a condensation reaction, and then subjected it to Polyethylene glycol (PEG) modification and ultrasonic nanocrystalline treatment to make it suitable forin vivophotothermal therapy applications. The conjugated polymer demonstrated good biocompatibility and photothermal conversion ability and was shown in cell experiments to be effective in killing tumor cells after laser irradiation. In addition, the conjugated polymer-based photothermal therapy, guided by photoacoustic real-time imaging and mediated by laser irradiation, of a tumor-bearing mouse model could effectively inhibit the growth of tumor tissue and demonstrated goodin vivobiosafety. Thus, photothermal therapy based on the conjugated polymer synthesized in this study provides a new idea and strategy for the treatment of lung cancer.

[System construction of early warning for ecological security at cultural and natural heritage mixed sites and its application: a case study of Wuyishan Scenery District].

This paper proposed a new concept of ecological security for protection by a comprehensive analysis of the contents and standards of world heritage sites. A frame concept model named "Pressure-State-Control" for early warning of ecological security at world heritage mixed sites was constructed and evaluation indicators of this frame were also selected. Wuyishan Scenery District was chosen for a case study, which has been severely disturbed by natural and artificial factors. Based on the frame model of "Pressure-State-Control" and by employing extension analysis, the matter-element model was established to assess the ecological security status of this cultural and natural world heritage mixed site. The results showed that the accuracy of ecological security early warning reached 84%. Early warning rank was I level (no alert status) in 1997 and 2009, but that in 2009 had a higher possibility to convert into II level. Likewise, the early-warning indices of sensitive ranks were different between 1997 and 2009. Population density, population growth rate, area index for tea garden, cultivated land owned per capita, level of drought, and investment for ecological and environmental construction were the main limiting factors to hinder the development of ecological security from 2009 to future. In general, the status of Wuyishan Scenery District ecological security was relatively good and considered as no alert level, while risk conditions also existed in terms of a few early-warning indicators. We still need to pay more attention to serious alert indicators and adopt effective prevention and control measures to maintain a good ecological security status of this heritage site.

[Chemical constituents from Salvia przewalskii Maxim].

The investigation on Salvia przewalskii Maxim was carried out to find the relationship of the constituents and their pharmacological activities. The isolation and purification were performed by various chromatographies such as silica gel, Sephadex LH-20, RP-C18 column chromatography, etc. Further investigation on the fraction of the 95% ethanol extract of Salvia przewalskii Maxim yielded przewalskin Y-1 (1), anhydride of tanshinone-II A (2), sugiol (3), epicryptoacetalide (4), cryptoacetalide (5), arucadiol (6), 1-dehydromiltirone (7), miltirone (8), cryptotanshinone (9), tanshinone II A (10) and isotanshinone-I (11). Their structures were elucidated by the spectral analysis such as NMR (Nuclear Magnetic Resonance) and MS (Mass Spectrometry). Compound 1 is a new compound. Compounds 4 and 5 are mirror isomers (1 : 3). Compounds 4, 5, 6, 8, 11 were isolated from Salvia przewalskii Maxim for the first time.

[Study on anti-HIV-1 activities of composite extract from salvia yunnanensis].

OBJECTIVE: To explore and evaluate the activities of composite extract from Salvia Yunnanensis and in cell cultures (DS-MEF) for inhibition of human immuno-deficiency virus type 1 (HIV-1) in vitro and in cell cultures. METHODS: The inhibitory activity of DS-MEF on HIV-1 reverse transcriptase (RT), protease (PR) and integrase (IN) were detected in vitro with radionuclide 3H incorporation, fluorescence assay and enzyme-linked immunosorbent assay respectively. The human T-lymphocyte MT-4 cell line, human T-lymphocyte H 9 cell line chronically infected with HIV-1 IIIB, and the fresh peripheral blood mononuclear cell (PBMC) of healthy persons as well as the laboratory passed HIV-1 IIIB and the clinically isolated HIV-1 AZT sensitive 018a or resistant 018c infected cell cultures were used for evaluating the cytotoxicities and inhibitory activities of DS-MEF on HIV-1 P 24 antigen. The acute toxicities of DS-MEF on KM mice were determined by gastric gavages and intraperitoneal injections with various dosages. RESULTS: The IC50 of DS-MEF for inhibiting HIV-1 IN, RT and PR were 2.59 +/- 0.50 mg/L, 27.39 +/- 11.18 mg/L and 9.38 +/- 2.45 mg/L respectively. In MT-4 cell cultures infected with HIV-1 III, TC50 were 13.19 +/- 6.07 mg/L, IC50 and SI of anti-HIV-1 activity were 0.224 +/- 0.163 mg/L and 58.7; in chronically infected H 9 cell cultures, TC50 were 18.11 +/- 9.84 mg/L, IC50 on HIV-1 P 24 antigen and SI were l7.230 +/- 21.114 mg/L and 1.1 respectively; TC50 in HIV-1 infected PBMC cultures were 288.70 +/- 0.08 mg/L; IC50 on AZT sensitive HIV-1 018a: 26.42 +/- 11.16 mg/L, and SI: 10.9; On AZT resistant HIV-1 018c, IC50: 27.87 +/-5.35 mg/L, and SI: 10.4. Moreover, DS-MEF showed synergistic effect with AZT or nevirapine (NVP) on HIV-1 IIIB in MT-4 cell cultures, the respective combination index was 0.78 or 0.67. DS-MEF showed no acute toxicity in KM mice with the dosage up to 20 g/kg via gastrogavage, and the 50% lethal dose (LD50) via intraperitoneal injection was 1.18 g/kg. CONCLUSION: DS-MEF is a promising anti- HIV-1 agent with low toxicity in mice and possesses multi-targets and effective activities.