Lu Xiaolei,Jia Jian,Ye Zhengmao,Du Peng,Chen Heng,Wu Jiaming,Cheng Xin
Nitrogenous strength enhancer is an organic chemical additive, which is popularly used to regulate cement hydration and improve cement properties. In this work, the effect of N, N-di(hydroxyethyl)glycine (bicine) on the hydration process and the properties of Portland cement were systematically investigated. The results obtained indicate that bicine significantly changes the morphology of portlandite crystals from a parallel-stacked lamellar shape to a distorted one and also decreases the pore size of the hardened cement paste at early age. The C–S–H phase in the hardened cement paste presents a higher Ca/Si ratio when adding bicine. Additionally, low doses of bicine can accelerate the hydration of C 3 A and C 3 S at lower dosage and promote the conversion of AFt to AFm. Thus, the mechanical performance would increase 30.9% and 13.6% at 3 d and 7 d only with 0.03% bicine, respectively. However, adding excessive bicine is not beneficial for the strength development in the early and late ages.
Weimin Fang,Jinghao Wang,Xiaocong Ma,Ni Shao,Kunlin Ye,Dong Zhang,Changzheng Shi,Liangping Luo
Background Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations’ antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib.Materials and Methods Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds.Results The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI).Conclusion Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.
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