Preparation of 4-sulfonylcalix6arene-modified cotton for uranium contamination removal / 中国辐射卫生

Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.

Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.

Antigen presentation and T cell activation by dendritic cells in radiation damage / 中国辐射卫生

@#<b>Objective</b> To explore dendritic cells (DCs)-mediated antigen presentation for radiation-injured cells by using the <i>in vitro</i> cell co-culture technology to simulate the <i>in vivo </i>microenvironment of the lung tissue. <b>Methods</b> ⁶⁰Co γ-irradiated mouse lung epithelial cells (MLE-12) were cultured with bone marrow-derived DCs and/or splenic T lymphocytes for 48 hours. Flow cytometry was used to measure the expression levels of costimulatory molecules (CD80/86) and antigenic peptide recognition complexes (the major histocompatibility complex [MHC] class Ⅰ/Ⅱ) on DCs and T cell activation markers (CD69/28/152) as well as the numbers of CD4⁺ and CD8⁺ T cells. <b>Results</b> ⁶⁰Co γ irradiation significantly increased the apoptosis rate of MLE-12 cells in a dose-dependent manner, and significantly stimulated the expression of CD80/86 and MHC Ⅱ on DCs, without direct activation of T cells. After γ (6 Gy)-irradiated MLE-12 cells were co-cultured with DCs and T lymphocytes for 48 h, there were significant increases in the expression of CD69 and CD28 on T cells, the numbers of CD4⁺ and CD8⁺ T cells, and the expression of CD86 and MHC I on DCs, as compared with the control groups. <b>Conclusion</b> Radiation-injured cells can stimulate antigen presentation by DCs and activate T cells.

Role of complement in radiation-induced lung injury / 中国辐射卫生

@#<b>Objective</b> To investigate the role of complement in radiation-induced lung injury in mice after chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy. <b>Methods</b> C57BL/6 mice underwent chest irradiation with ⁶⁰Co γ-rays at a single dose of 20 Gy, followed by observation for the inflammatory reaction of the lung tissue in the early stage (within 15 d) and pulmonary fibrosis in the later stage (30 and 180 d). Enzyme-linked immunosorbent assay was used to measure the levels of C2, C3a, C4, and C5b-9 in the lung tissues at 1, 3, 7, 15, 30, and 180 d after irradiation. The expression of complement mRNA in BEAS-2B cells after irradiation was determined using RT-PCR. <b>Results</b> Radiation-induced lung injury in micepresented as inflammatory response in the early stage and fibrosis in the late stage. Complement C2, C4, and C5b-9 complexes were increased in the early period (3 or 7 d) after irradiation (<i>P</i> < 0.05), which might be associated with the inflammatory response induced by irradiation. During 3 to 180 d, complement C3a was significantly higher in the irradiated mice than in the control mice, suggesting a close relationship between C3a and radiation-induced lung injury. The irradiated cells showed increased mRNA expression of C2 and C3, with no changes in the mRNA levels of C4 and C5. <b>Conclusion</b> Different complement proteins have varying responses to radiation-induced lung injury, among which C3a is closely related to radiation-induced lung injury, suggesting that regulating C3a and its receptors may be a new way to prevent and treat radiation-induced lung injury.