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| 1 | Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial—mesenchymal transition via directly targeting TGFβR1显示文摘As the most aggressive breast cancer,triple-negative breast cancer(TNBC) is still incurable and very prone to metastasis.The transform growth factor β(TGF-β)-induced epithelial—mesenchymal transition(EMT) is crucially involved in the growth and metastasis of TNBC.This study reported that a natural compound isotoosendanin(ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia.ITSN can directly interact with TGF-β receptor type-1(TGFβR1) and abrogated the kinase activity of TGFβR1,thereby blocking the TGF-β-initiated downstream signaling pathway.Moreover,the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1.Furthermore,Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1.Additionally,ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1(PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment.Our findings not only highlight the key role of TGFβR1 in TNBC metastasis,but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis.Moreover,this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor. | Jingnan Zhang Ze Zhang Zhenlin Huang Manlin Li Fan Yang Zeqi Wu Qian Guo Xiyu Mei Bin Lu Changhong Wang Zhengtao Wang Lili Ji | 2023 | Acta Pharmaceutica Sinica B2023，13，7： | 1 |
| 2 | Polybenzoxazine/organosilicon composites with low dielectric constant and dielectric loss显示文摘The evolution of electronic communication technology raises higher requirements for low dielectric constant(low-k)materials.For this,a benzoxazine functional organosilicon(HP-aptes)with dense Si—O—Si crosslinking networks and large sterically hindered tert-butyl groups was prepared by the sol–gel method.Then,a series of polybenzoxazine composites(PPHP)were prepared from intrinsically low dielectric constant bis-functional benzoxazine monomer(P-aptmds)and HP-aptes.The double crosslinking networks of polybenzoxazine and organosilicon further increased the crosslinking density and decreased the dipole density of composites,which endowed the composites with enhanced low-k properties.When the content of HP-aptes is 30%(mass),the crosslinking density was 2.05×10^(-3)mol·cm^(-3),while that of PP-aptmds was 3.31×10^(-3)mol·cm^(-3).In addition,the dielectric constant and dielectric loss of PPHP composite at 1 MHz could reach 2.61 and 0.0056,respectively. | Manlin Yuan Xin Lu Xiaoyun Ma Hao Lin Angui Lu Liyan Shao Zhong Xin | 2023 | Chinese Journal of Chemical Engineering2023，64，12： | 0 |
| 3 | Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment显示文摘Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL. | Sichao Liang Yunshuo Li Zhenping Guo Manlin Lu Xin Li Jia Xu Wenjing Chen Juanjuan Gao Haijin Yi | 2024 | Journal of Otology2024，19，1： | 0 |
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