Academic literature on the topic 'Gao deng xue xiao'

We remark that the schemes [S. Gaertner, C. Kurtsiefer, M. Bourennane and H. Weinfurter, Phys. Rev. Lett.98 (2007) 020503; H. Takesue and K. Inoue, Phys. Rev. A74 (2006) 012315; L. Hsu and C. Li, Phys. Rev. A71 (2005) 022321; F. Yan and T. Gao, Phys. Rev. A72 (2005) 012304; L. Xiao, G. Long, F. Deng and J. Pan, Phys. Rev. A69 (2004) 052307; M. Hillery, V. Bužek and A. Berthiaume, Phys. Rev. A59 (1999) 1829] are not secret sharing schemes as claimed.

BackgroundOutcomes for high grade serous ovarian cancer (HGSOC) patients have remained dismal due to the inevitable development of chemotherapy resistance with recurrent disease.1 In order to better tailor treatment approaches and uncover opportunities for novel treatments, we need to better understand factors contributing to chemotherapy resistance. Recent studies have shown that immune-related gene expression profiles may serve as prognostic indicators of response to chemotherapy and clinical outcomes in solid tumors, including ovarian cancer.2–7 Moreover, immunologic factors have been shown to mediate chemotherapy resistance8 Reports in the literature show that common ovarian cancer therapeutics, including chemotherapy, PARP inhibitors, and bevacizumab, modulate tumor cell expressed PD-L1 levels through immunologic signaling pathways.9–12 However, very little research has addressed the effect of these treatments on other immune ligands or the differences in immunologic responses between platinum-sensitive and platinum-resistant HGSOC cell lines.MethodsThe HGSOC cell lines OVCAR4 (naturally platinum-resistant), PEO1 and PEO4 (matched platinum-sensitive and -resistant lines from the same patient), were treated with common ovarian cancer therapeutics (carboplatin/paclitaxel, olaparib, and bevacizumab), in the presence or absence of peripheral blood mononuclear cells. Western blot was employed to identify levels of immune ligands of interest and a proteome profiler was used to detect broad immunologic changes in response to standard of care therapeutics.ResultsOlaparib and bevacizumab treatment strikingly upregulated levels of tumor cell expressed immune ligands ICOSL and PVRL2. Platinum status or presence of an immune component had no bearing on the effect. Moreover, blockade of PVRL2 using siRNA or monoclonal antibodies suppressed STAT3 signaling. When examining the effect of these therapeutics on cytokine levels in HGSOC cell lines treated in immune cell co-culture, OVCAR4 cells displayed marked changes in cytokine levels, particularly CXCL10, CXCL12, SERPINE1, IL1A, and IL1RA. While PEO1 and PEO4 cells displayed more subtle cytokine changes compared to OVCAR4 cells, differences in basal levels and treatment responses were observed between the platinum-sensitive and -resistant lines, most strikingly higher basal levels of SERPINE1 and CCL5/RANTES in PEO4 cells, and a robust increase in IL8 levels in response to chemotherapy in only PEO1 cells and not PEO4.ConclusionsIn conclusion, common ovarian cancer chemotherapeutics and targeted agents induce tumor cell intrinsic immunologic effects that could potentially be exploited as combinatorial therapeutic targets. Differences in immunologic responses may help define platinum-sensitive and -resistant disease. These results will require further exploration in immune-competent mouse models and human HGSOC tissue.ReferencesCortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol 2018;81(1):17–38.James NE, Miller K, LaFranzo N, Lips E, Woodman M, Ou J, Ribeiro JR. Immune modeling analysis reveals immunologic signatures associated with improved outcomes in high grade serous ovarian cancer. Front Oncol 2021;11:622182.Liu R, Hu R, Zeng Y, Zhang W, Zhou H-H. Tumour immune cell infiltration and survival after platinum-based chemotherapy in high-grade serous ovarian cancer subtypes: a gene expression-based computational study. EBioMedicine 2020;51:102602.Liu J, Meng H, Nie S, Sun Y, Jiang P, Li S, et al. Identification of a prognostic signature of epithelial ovarian cancer based on tumor immune microenvironment exploration. Genomics. 2020.Ding J, Zhang Q, Chen S, Huang H, He L. Construction of a new tumor immunity-related signature to assess and classify the prognostic risk of ovarian cancer. Aging (Albany, NY). 2020;12.Wu Y, Xia L, Zhao P, Deng Y, Guo Q, Zhu J, et al. Immune profiling reveals prognostic genes in high-grade serous ovarian cancer. Aging (Albany, NY). 2020;12(12):11398–11415.Montfort A, Owen S, Piskorz AM, Supernat A, Moore L, Al-Khalidi S, et al. Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma. Br J Cancer 2020;122(12):1803–1810.Liu W, Wang Y, Xie Y, Dai T, Fan M, Lu C, Zou Y. Cisplatin remodels the tumor immune microenvironment via the transcription factor EB in ovarian cancer. Cell Death Discov. 2021;7(1):136.Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M. Chemotherapy induces programmed cell death-Ligand 1 overexpression via the nuclear factor-κB to foster an immunosuppressive tumor microenvironment in Ovarian cancer. Cancer Res 2015;75(23):5034–45.Jiao S, Xia W, Yamaguchi H, Wei Y, Chen M-K, Hsu J-M, et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res 2017;23(14):3711–3720.Xue C, Xu Y, Ye W, Xie Q, Gao H, Xu B, et al. Expression of PD-L1 in ovarian cancer and its synergistic antitumor effect with PARP inhibitor. Gynecol Oncol 2020;157(1):222–233.Zhang L, Chen Y, Li F, Bao L, Liu W. Atezolizumab and bevacizumab attenuate cisplatin resistant Ovarian cancer cells progression synergistically via suppressing epithelial-Mesenchymal transition. Front Immunol 2019;10:867.

Abstract Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increased lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly altered the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolished stress-induced metastasis, indicating their critical role. Chronic stress shifted neutrophils’ normal circadian rhythm, and, via glucocorticoid release, caused increased neutrophil extracellular trap (NET) formation. Importantly, in mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress failed to increase NETs and metastasis. Furthermore, digesting NETs with deoxyribonuclease (DNase) I prevented chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease. Citation Format: Xue-Yan He, Yuan Gao, David Ng, Evdokia Michalopoulou, Shanu George, Jose M. Adrover, Lijuan Sun, Jean Albrengues, Juliane Daßler-Plenker, Xiao Han, Ledong Wan, Xiaoli S. Wu, Longling S. Shui, Yu-Han Huang, Bodu Liu, Chang Su, David L. Spector, Christopher R. Vakoc, Linda VanAelst, Mikala Egeblad. Chronic stress causes metastasis via neutrophil-mediated changes to the microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5517.

The molten salt CO2 capture and electrochemical transformation (MSCC-ET) process has been demonstrated as an effective approach to capturing and converting CO2 into oxygen and C/CO [1-2]. The effective CO2 capture and electrochemical conversion rely on the high-temperature molten carbonate electrolytes and the cost-effective inert oxygen-evolution anode. In recent years, we have focused on the electrolyte engineering to modulate the reactions at both the cathode and anode as well as the CO2 capture efficiency [3-4]. Besides, we insist on developing iron- and nickel-base oxygen-evolution inert anodes in terms of revealing the fundamental principles and basic guidelines for choosing proper materials and fabrication processes [5]. By doing so, we can prepare functional carbon materials or CO at the cathode with a high current efficiency of over 90%, and produce oxygen at the inert anode. In addition, the kilo-ampere scale electrolyzer was built to produce oxygen, carbon or CO with an energy efficiency of over 50%. Therefore, the molten carbonate CO2 electrolyzer shows its potential to convert CO2 on the Mars to produce oxygen and fuels to support the future exploration of outer space. References [1] H. Y. Yin, D. H. Wang*, et al., Capture and electrochemical conversion of CO2 to value-added carbon and oxygen by molten salt electrolysis. Energy & Environmental Science, 2013, 6: 1538-1545. [2] R. Jiang, M. X. Gao, X. H. Mao, D. H. Wang*. Advancements and potentials of molten salt CO2 capture and electrochemical transformation (MSCC-ET) process, Current Opinion in Electrochemistry, 2019, 17: 38-46. [3] B. W. Deng, J. J. Tang, X. H. Mao, Y. Q. Song, H. Zhu, W. Xiao, D. H. Wang*. Kinetic and Thermodynamic Characterization of Enhanced Carbon Dioxide Absorption Process with Lithium Oxide-Containing Ternary Molten Carbonate, Environmental Science & Technology, 2016, 50(19): 10588-10595. [4] Z. S Yang, B. W. Deng, K. F. Du, H. Y. Yin*, D. H. Wang*, A general descriptor for guiding the electrolysis of CO2 in molten carbonate, 2022, in press. [5] P. L. Wang, K. F. Du, Y. P. Dou, H. Zhu, D. H. Wang*, Corrosion behaviour and mechanism of nickel anode in SO42- containing molten Li2CO3-Na2CO3-K2CO3. Corrosion Science 2022, 166. Figure 1

Abstract There is emerging evidence that exposure to chronic stress is associated with increased risk of metastasis and poor survival in cancer patients. However, the underlying molecular and cellular mechanisms responsible for the effects of stress on tumor progression remain unclear. To determine how stress promotes metastasis, we established new mouse models in which multiple chronic stress exposure promoted breast cancer metastasis to the lungs. We found that chronic stress generates a pro-metastatic lung microenvironment with e.g., reduced T cell infiltration and increased extracellular matrix (ECM) deposition and neutrophil infiltration. Among them, neutrophils were required for these changes as their depletion abolished the pro-metastatic effects of stress and normalized the lung tumor microenvironment. Mechanistically, we analyzed neutrophils from chronically stressed mice and identified dramatically altered transcriptomes, including increased expression of several glucocorticoid receptor regulated genes. Phenotypically, neutrophils from stress exposed mice exhibited increased ROS production, and an increased ability to inhibit T cell activation and to form spontaneous neutrophil extracellular traps (NETs). The stress-associated changes to neutrophils were dependent on glucocorticoid receptor (GR) signaling as neutrophil-specific GR knockout mice showed no increase in NET-formation, a normalized lung microenvironment and no increase in lung metastasis upon stress exposure. Among the changes in the neutrophils caused by stress exposure, we found that the formation of pro-metastatic NETs was critical as directly digesting NETs with DNase I prevented stress-induced metastasis and normalized the lung microenvironment. In sum, this work shows that chronic stress exposure causes a glucocorticoid-mediated increase in NET formation and that NETs are critical drivers in the establishment of a stress-induced, metastasis-promoting microenvironment. Targeting NETs could be an important strategy to prevent metastatic recurrence in cancer patients, many of whom will experience stress due to their cancer diagnosis and subsequent treatments. Citation Format: Xue-Yan He, David Ng, Yuan Gao, Evdokia Michalopoulou, Shanu George, Jose M. Adrover, Lijuan Sun, Jean Albrengues, Ledong Wan, Xiao Han, Christopher Vakoc, Linda Van Aelst, Mikala Egeblad. Untangling the connection between stress and metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 62.

Recently, sulfonamides have been shown to be promising electrolyte components due to their high chemical and electrochemical stability in lithium batteries [1, 2]. The electrolyte stability becomes critical when applying high voltage and/or utilizing Ni-rich layered oxides in high energy density lithium-ion batteries. Another approach to successful Ni-rich cathode performance is to develop a stable and effective cathode electrolyte interphase (CEI). Given the success of sultones and sulfates in this regard [3, 4], it is hypothesized that nitrogen analogs, like sulfonamides, could be tailored to provide a similar benefit. Indeed, Yim et al. [5, 6] have shown that N,N,N’,N’-tetraethylsulfamide (TES) forms a CEI on NMC811 that imparts high voltage cycling stability and less cathode corrosion. Our earlier studies of TES with Ni-rich NCA also formed a favorable CEI and these results are the topic of this presentation. Herein, we examine the performance of 0 - 4 wt.% TES in our commercially available, high power INR18650-P28A. These cells contain a composite SiO/graphite anode in addition to a Ni-rich cathode. As shown in Fig 1, TES significantly decreased the impedance of the cathode interface after conditioning compared to the control electrolyte. Thereafter, cells containing up to 2%TES show improved capacity retention during long-term high-rate cycling (+1C/-80W). Part of this success was due to a suppression of resistance growth during cycling by TES. Fast charge cycling (+3C/-2C), however, was moderately impaired with increased TES. Considering the largely reduced impedance of the cathode, fast-charge performance may have suffered due to anode rate limitations. These results will be discussed as well as gas generation, storage performance, and additional rate and cycling tests. [1] Shuting Feng, Mingjun Huang, Jessica R. Lamb, Wenxu Zhang, Ryoichi Tatara, Yirui Zhang, Yun Guang Zhu, Collin F. Perkinson, Jeremiah A. Johnson, Yang Shao-Horn. Chem, 5, 2630-2641 (2019) [2] Weijiang Xue, Mingjun Huang, Yutao Li, Yun Guang Zhu, Rui Gao, Xianghui Xiao, Wenxu Zhang, Sipei Li, Guiyin Xu, Yang Yu, Peng Li, Jeffrey Lopez, Daiwei Yu, Yanhao Dong, Weiwei Fan, Zhe Shi, Rui Xiong, Cheng-Jun Sun, Inhui Hwang, Wah-Keat Lee, Yang Shao-Horn, Jeremiah A. Johnson, Ju Li. Nature Energy, 6, 495-505 (2021) [3] Koji Abe, Manuel Colera, Kei Shimamoto, Masahide Kondo, Kazuhiro Miyoshi. Journal of Electrochemical Society, 161 (6) A863-A870 (2014) [4] Jian Xia, N. N. Sinha, L. P. Chen, J. R. Dahn. Journal of Electrochemical Society, 161 (3) A264-A274 (2014) [5] Kwangeun Jung, Taeeun Yim. Journal of Alloys and Compounds, 834,155155 (2020) [6] Ji Won Kim, Kwangeun Jung, Taeeun Yim. Journal of Mater. Sci & Tech. 86, 70-76 (2021) Figure 1

Abstract Background: As the most prevalent internal decorations in mammalian mRNA, N6-methyladenosine (m6A) has been reported to be involved in many physiological and pathological processes, including acute myeloid leukemia (AML). METTL3 and METTL14, the well-recognized m6A methyltransferase complex, contribute to AML. METTL16 is a recently identified m6A methyltransferase that has been reported to deposit m6A in a few targets. While, unlike METTL3/14, the biological functions of METTL16 are largely unknown. Here, we explored the function and mechanism of METTL16 in AML pathogenesis and evaluated its therapeutic potential for AML treatment. Methods: We performed CRISPR-Cas9 screen to evaluate the dependency of METTL16 in AML cells. We created METTL16 knockout (KO) cells and conditional KO mice to evaluate its role in leukemogenesis and normal hematopoiesis. We employed bone marrow transplantation (BMT), xenograft, and AML patient-derived xenograft (PDX) models to determine its role in AML development and progression. To identify the targets of METTL16, we performed m6A-seq and RNA-seq, followed m6A-qPCR, CLIP-qPCR, in vitro methyltransferase assays and RNA stability assays. To examine the effect of METTL16 on branched chain amino acid (BCAA) metabolism, we performed metabolic profiling with 13C, 15N-leucine. Results: CRISPR-Cas9 screen showed METTL16 is one of the most essential genes for the survival of AMLs. The AML cells display more robust dependency on METTL16 than METTL3/14. We found METTL16 is highly expressed in AML patients compared to healthy controls. METTL16 KO significantly inhibited AML cell proliferation, promoted cell apoptosis and myeloid differentiation in vitro, which could be totally reversed by forced expression of wild-type METTL16, but not catalytic-dead mutant. METTL16 depletion dramatically inhibited AML progression and prolonged survival of recipient mice in the BMT, xenograft and PDX models. In addition, METTL16 is highly expressed in LSCs contrast to leukemic bulk cells and METTL16 KO significantly attenuates LSC self-renewal in vitro and in vivo. By contrast, the role of METLL16 is largely spared in normal hematopoietic cells. Via integrated analysis of m6A-seq data and RNA-seq data, we identified two bona fide targets of METTL16, BCAT1 and BCAT2, which encode two critical BCAA transaminases in BCAA biosynthesis pathway. METTL16 promotes the expression of BCAT1 and BCAT2 via an m6A dependent manner. Metabolomics with 13C, 15N-leucine tracing showed that METTL16 KO results in suppressed pools of TCA cycle intermediates, some non-essential amino acids and nucleotides. Conclusion: We uncover a tumor-promoting role of METTL16 in AML and LSC self-renewal via reprogramming BCAA metabolism, in which METTL16 functions as an m6A methyltransferase to regulate expression of BCAT1 and BCAT2. Our data suggest that METTL16 is an attractive target for AML therapy. Citation Format: Li Han, Lei Dong, Keith Leung, Zhicong Zhao, Yangchan Li, Ying Qing, Jianhuang Xue, Chao Shen, Zhenhua Chen, Lei Gao, Kitty Wang, Keren Zhou, Wei Li, Brandon Tan, Zheng Zhang, Xi Qin, Rui Su, Xiaolan Deng, Jianjun Chen. METTL16 drives leukemogenesis and maintains leukemia stem cell self-renewal via reprogramming BCAA metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3617.

Lithium-ion batteries (LIBs) have gained increasing importance in energy storage systems, driven by the growing demands of grid storage, automotive, and portable consumer applications. To meet the need for high energy density batteries, one promising approach involves the utilization of high capacity layered transition metal oxide cathodes, such as nickel-rich LiNi0.8Mn0.1Co0.1O2 (NMC811), which can deliver a high reversible specific capacity of over 180 mAh·g-1 [1,2]. However, due to the structural and interfacial instability[3], nickel-rich NMC cathode still faces challenges in long-term galvanostatic cycling. For these reasons, design of novel electrolyte formulations, which enable formation of an effective cathode electrolyte interphase (CEI), is highly desirable. Recent studies have highlighted the cross-talk between the cathode and anode, indicating that the evolution of the solid electrolyte interphase (SEI) can impact the formation of the CEI[4]. Thus, establishing an effective SEI/CEI pair is essential for achieving long-term cycling of nickel-rich NMC cathode-based cells. Electrolyte optimization plays a crucial role in facilitating the formation of a desirable SEI/CEI pair, leading to an improved cell performance and longevity. Lithium (difluoromethanesulfonyl)(trifluoro-methanesulfonyl)imide (LiDFTFSI) has proven to be promising in solid-polymer-electrolyte batteries due to the good SEI/CEI formation ability and suppressed Al-dissolution[5]. Additionally, LiDFTFSI exhibits also good compatibility with Li-metal batteries[6], heralding promising applications in Li-ion batteries. However, there is lack of systematic research investigating the potential impact of LiDFTFSI on the cathode as well as on resulting CEI formation and dynamics. In this work, we demonstrated enhanced galvanostatic cycling performance of NMC811||graphite cells achieved by utilizing LiDFTFSI and lithium hexafluorophosphate (LiPF6) in a blended salt organic carbonate-based electrolyte formulation. Comprehensive electrochemical and post mortem analysis revealed that the LiDFTFSI alone can effectively mitigate the structural changes in the NMC811 electrode by facilitating the formation of modified CEI. However, the continued growth of an inhomogeneous CEI, caused by the cross-talk effect between electrodes, adversely affected long-term cycling stability. To address this, vinylene carbonate (VC) was introduced to the electrolyte. Synergistic effect with LiDFTFSI leads to the formation of effective and uniform SEI and CEI. As a result, 720 charge/discharge cycles were achieved in NMC811||graphite cells with LiDFTFSI and VC containing electrolytes at 1C while maintaining 80% state-of-health (SOH80%). References [1] R. Schmuch, R. Wagner, G. Hörpel, T. Placke, M. Winter, Nature Energy 2018, 3, 267–278. [2] W. Xue, M. Huang, Y. Li, Y. G. Zhu, R. Gao, X. Xiao, W. Zhang, S. Li, G. Xu, Y. Yu, P. Li, J. Lopez, D. Yu, Y. Dong, W. Fan, Z. Shi, R. Xiong, C.-J. Sun, I. Hwang, W.-K. Lee, Y. Shao-Horn, J. A. Johnson, J. Li, Nature Energy 2021, 6, 495–505. [3] K. Guo, S. Qi, H. Wang, J. Huang, M. Wu, Y. Yang, X. Li, Y. Ren, J. Ma, Small Science 2022, 2, 2100107. [4] S. Fang, D. Jackson, M. L. Dreibelbis, T. F. Kuech, R. J. Hamers, Journal of Power Sources 2018, 373, 184–192. [5] H. Zhang, U. Oteo, X. Judez, G. G. Eshetu, M. Martinez-Ibañez, J. Carrasco, C. Li, M. Armand, Joule 2019, 3, 1689–1702. [6] L. Qiao, U. Oteo, M. Martinez-Ibañez, A. Santiago, R. Cid, E. Sanchez-Diez, E. Lobato, L. Meabe, M. Armand, H. Zhang, Nat. Mater. 2022, 21, 455–462.

В данной работе продемонстрирована возможность применения ИК-микроспектроскопии для многомерной визуализации и анализа интеграции с нативными твердыми тканями зуба человека нового поколения биомиметических материалов, воспроизводящих минералорганический комплекс эмали и дентина.На основе ИК-картирования интенсивности конкретной функциональной молекулярной группы с использованием синхротронного излучения найдены и визуализированы характеристические особенности биомиметического переходного слоя в межфазной области эмаль/стоматологический материал и определено расположение функциональных групп, отвечающих процессам интеграции биомиметического композита REFERENCES Rohr N., Fischer J. Tooth surface treatment strategies for adhesive cementation // The Journal of Advanced Prosthodontics, 2017, v. 9(2), pp. 85–92. https://doi.org/10.4047/jap.2017.9.2.85 Pereira C. N. de B., Daleprane B., Miranda G. L. P. de, Magalhães C. S. de, Moreira A. N. Ultramorphology of pre-treated adhesive interfaces between self-adhesive resin cement and tooth structures // Revista de Odontologia da UNESP, 2017, v. 46(5), pp. 249–254. https://doi.org/10.1590/1807-2577.04917 Temel U. B., Van Ende A., Van Meerbeek B., Ermis R. B. Bond strength and cement-tooth interfacial characterization of self-adhesive composite cements //American Journal of Dentistry, 2017, v. 30(4), pp. 205–211. Watson T. F., Atmeh A. R., Sajini S., Cook R. J., Festy F. Present and future of glass-ionomers and calcium-silicate cements as bioactive materials in dentistry: Biophotonics-based interfacial analyses in health and disease // Dental Materials, 2014, v. 30(1), pp. 50–61. https://doi.org/10.1016/j.dental.2013.08.202 Pontes D. G., Araujo C. T. P., Prieto L. T., de Oliveira D. C. R. S., Coppini E. K., Dias C. T. S., Paulillo L. A. M. S. Nanoleakage of fi ber posts luted with different adhesive strategies and the effect of chlorhexidine on the interface of dentin and self-adhesive cements // General Dentistry, 2015, v. 63(3), pp. 31–37. PMID: 25945761 Teaford M. F., Smith M. M., Ferguson W. J. Development, Function and Evolution of Teeth. Cambridge University Press, 2007, 328 p. Dorozhkin S. V. Hydroxyapatite and Other Calcium Orthophosphates: Bioceramics, Coatings and Dental Applications [Hardcover]. Nova Science Publishers, Inc New York, 2017, 462 p. URL: https://istina.msu.ru/publications/book/58538935/ Uskoković V. Biomineralization and biomimicry of tooth enamel. Non-Metallic Biomaterials for Tooth Repair and Replacement. Elsevier, 2013, pp. 20–44. URL:http://linkinghub.elsevier.com/retrieve/pii/B9780857092441500021 Niu L., Zhang W., Pashley D. H., Breschi L., Mao J., Chen J., Tay F. R. Biomimetic remineralization of dentin // Dental Materials, 2014, v. 30(1), pp. 77–96. https://doi.org/10.1016/j.dental.2013.07.013 Cao C., Mei, Li Q., Lo E., Chu C. Methods for Biomimetic Mineralisation of Human Enamel: A Systematic Review // Materials, 2015, v. 8(6), pp. 2873–2886. https://doi.org/10.3390/ma8062873 Chen L., Yuan H., Tang B., Liang K., Li J. Biomimetic remineralization of human enamel in the presence of polyamidoamine dendrimers in vitro // Caries Research, 2015, v. 49(3), pp. 282–290. https://doi.org/10.1159/000375376 Seredin P. V., Goloshchapov D. L., Gushchin M. S., Ippolitov Y. A., Prutskij T. The importance of the biomimetic composites components for recreating the optical properties and molecular composition of intact dental tissues. // Journal of Physics: Conference Series, 2017, v. 917(4), pp. 042019. https://doi.org/10.1088/1742-6596/917/4/042019 Xia Z. Biomimetic Principles and Design of Advanced Engineering Materials. John Wiley & Sons, 2016, 321 p. Dorozhkin S. V. Self-Setting Calcium Orthophosphate Formulations: Cements, Concretes, Pastes and Putties // International Journal of Materials and Chemistry, 2012, v. 1(1), pp. 1–48. https://doi.org/10.5923/j.ijmc.20110101.01 Li H., Gong M., Yang A., Ma J., Li X., Yan Y. Degradable biocomposite of nano calcium-defi cient hydroxyapatite-multi(amino acid) copolymer // International Journal of Nanomedicine, 2012, v. 7, pp. 1287–1295. https://doi.org/10.2147/IJN.S28978 Ruan Q., Zhang Y., Yang X., Nutt S., Moradian-Oldak J. An amelogenin–chitosan matrix promotes assembly of an enamel-like layer with a dense interface// Acta Biomaterialia, 2013, v. 9(7), pp. 7289–7297. https://doi.org/10.1016/j.actbio.2013.04.004 Yao, Shao H., Zhang Q. Development and Characterization of a Novel Amorphous Calcium Phosphate/Multi (Amino Acid) Copolymer Composite for Bone Repair // Journal of Biomaterials and Tissue Engineering, 2015, v. 5(5), pp. 387–390. https://doi.org/10.1166/jbt.2015.1321 Melo M. A. S., Weir M. D., Rodrigues L. K. A., Xu H. H. K. Novel calcium phosphate nanocomposite with caries-inhibition in a human in situ model // Dental Materials, 2013, v. 29(2), pp. 231–240. https://doi.org/10.1016/j.dental.2012.10.010 Wu X.-T., Mei M., Li Q.-L., Cao C., Chen-L., Xia R., Zhang Z.-H., Chu C. A Direct Electric Field-Aided Biomimetic Mineralization System for Inducing the Remineralization of Dentin Collagen Matrix // Materials, 2015, v. 8(12), pp. 7889–7899. https://doi.org/10.3390/ ma8115433 Barghamadi H., Atai M., Imani M., Esfandeh M. Effects of nanoparticle size and content on mechanical properties of dental nanocomposites: experimental versus modeling // Iranian Polymer Journal, 2015, v. 24. (10), pp. 837–848. https://doi.org/10.1007/s13726-015-0369-5 Wang H., Xiao Z., Yang J., Lu D., Kishen A., Li Y., Chen Z., Que K., Zhang Q., Deng X., Yang X., Cai Q., Chen N., Cong C., Guan B., Li T., Zhang X. Oriented and Ordered Biomimetic Remineralization of the Surface of Demineralized Dental Enamel Using HAP@ ACP Nanoparticles Guided by Glycine // Scientifi c Reports, 2017, v. 7(1), рр. 1-13. https://doi.org/10.1038/srep40701 Wu X., Zhao X., Li Y., Yang T., Yan X., Wang K. In situ synthesis carbonated hydroxyapatite layers on enamel slices with acidic amino acids by a novel twostep method // Materials Science & Engineering. C, Materials for Biological Applications, 2015, v. 54, pp. 150–157. httsp://doi.org/10.1016/j.msec.2015.05.006 Aljabo A., Abou Neel E. A., Knowles J. C., Young A. M. Development of dental composites with reactive fi llers that promote precipitation of antibacterial-hydroxyapatite layers // Materials Science and Engineering: C, 2016, v. 60, pp. 285–292. https://doi.org/10.1016/j.msec.2015.11.047 Wang P., Liu P., Peng H., Luo X., Yuan H., Zhang J., Yan Y. Biocompatibility evaluation of dicalcium phosphate/calcium sulfate/poly (amino acid) composite for orthopedic tissue engineering in vitro and in vivo // Journal of Biomaterials Science. Polymer Edition, 2016, v. 27(11), pp. 1170–1186. https://doi.org/10.1080/09205063.2016.1184123 Lübke A., Enax J., Wey K., Fabritius H.-O., Raabe D., Epple M. Composites of fl uoroapatite and methylmethacrylate-based polymers (PMMA) for biomimetic tooth replacement // Bioinspiration & Biomimetics, 2016, v. 11(3), pp. 035001. https://doi.org/10.1088/1748-3190/11/3/035001 Sa Y., Gao Y., Wang M., Wang T., Feng X., Wang Z., Wang Y., Jiang T. Bioactive calcium phosphate cement with excellent injectability, mineralization capacity and drug-delivery properties for dental bio- mimetic reconstruction and minimum intervention therapy. RSC Advances, 2016, v. 6(33), pp. 27349–27359. https://doi.org/10.1039/C6RA02488B Adachi T., Pezzotti G., Yamamoto T., Ichioka H., Boffelli M., Zhu W., Kanamura N. Vibrational algorithms for quantitative crystallographic analyses of hydroxyapatite-based biomaterials: II, application to decayed human teeth // Analytical and Bioanalytical Chemistry, 2015, v. 407(12), pp. 3343–3356. https://doi.org/10.1007/s00216-015-8539-z Mitić Ž., Stolić A., Stojanović S., Najman S., Ignjatović N., Nikolić G., Trajanović M. Instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue: A review // Materials Science and Engineering: C, 2017, v. 79, pp. 930–949. https://doi.org/10.1016/j.msec.2017.05.127 Optical spectroscopy and computational methods in biology and medicine / Ed. by Barańska M., Dordrecht: Springer, 2014, 540 p. URL: http://link.springer.com/10.1007/978-94-007-7832-0 Hędzelek W., Marcinkowska A., Domka L., Wachowiak R. Infrared Spectroscopic Identifi cation of Chosen Dental Materials and Natural Teeth // Acta Physica Polonica A, 2008, v. 114(2), pp. 471–484. https://doi.org/10.12693/APhysPolA.114.471 Vongsvivut J., Perez-Guaita D., Wood B. R., Heraud P., Khambatta K., Hartnell D., Hackett M. J., Tobin M. J. Synchrotron macro ATR-FTIR microspectroscopy for high-resolution chemical mapping of single cells // The Analyst, 2019, v. 144(10), pp. 3226–3238. https://doi.org/10.1039/c8an01543k Seredin P., Goloshchapov D., Ippolitov Y., Vongsvivut P. Pathology-specifi c molecular profi les of saliva in patients with multiple dental caries—potential application for predictive, preventive and personalised medical services // EPMA Journal, 2018, v. 9(2), pp. 195–203. https://doi.org/10.1007/s13167-018-0135-9 Dusevich V., Xu C., Wang Y., Walker M. P., Gorski J. P. Identifi cation of a protein-containing enamel matrix layer which bridges with the dentine–enamel junction of adult human teeth // Archives of Oral Biology, 2012, v. 57(12), pp. 1585–1594. https://doi.org/10.1016/j.archoralbio.2012.04.014 Seredin P. V., Kashkarov V. M., Lukin A. N., Goloshchapov D. L., Ippolitov Y. A. Research Hydroxyapatite Crystals and Organic Components of Hard Tooth Tissues Affected by Dental Caries Using Ftir-Microspectroscopy and Xrd-Microdiffraction // Condensed Matter and Interphases, 2013, v. 15(3), с. 224–231. URL: http://www.kcmf.vsu.ru/resources/t_15_3_2013_002.pdf Fattibene P., Carosi A., Coste V. D., Sacchetti A., Nucara A., Postorino P., Dore P. A comparative EPR, infrared and Raman study of natural and deproteinated tooth enamel and dentin // Physics in Medicine and Biology, 2005, v. 50(6), pp. 1095. https://doi.org/10.1088/0031-9155/50/6/004 Seredin P., Goloshchapov D., Kashkarov V., Ippolitov Y., Bambery K. The investigations of changes in mineral–organic and carbon–phosphate ratios in the mixed saliva by synchrotron infrared spectroscopy // Results in Physics, 2016, v. 6, pp. 315–321. https://doi.org/10.1016/j.rinp.2016.06.005 Goloshchapov D. L., Kashkarov V. M., Rumyantseva N. A., Seredin P. V., Lenshin A. S., Agapov B. L., Domashevskaya E. P. Synthesis of nanocrystalline hydroxyapatite by precipitation using hen’s eggshell // Ceramics International, 2013, v. 39(4), pp. 4539–4549. https://doi.org/10.1016/j.ceramint.2012.11.050 Goloshchapov D. L., Lenshin A. S., Savchenko D. V., Seredin P.V. Importance of defect nanocrystalline calcium hydroxyapatite characteristics for developing the dental biomimetic composites // Results in Physics, 2019, v. 13, pp. 102158. https://doi.org/10.1016/j.rinp.2019.102158 Nanci A. Ten Cate’s Oral Histology: Development, Structure, and Function. 8th ed., Elsevier Health Sciences, 2013, 400 p. Ippolitov Ju. A. Vozmozhnost’ povyshenija biologicheskoj tropnosti svetootverzhdaemoj bondingovoj sistemy dlja adgezii tverdyh tkanej zuba k plombirovochnomu material [The possibility of increasing the biological tropism of the lightcuring bonding system for adhesion of hard tooth tissues to the filling material]. Volgogradskij nauchno-medicinskij zhurnal, 2010, v. 4 (28), pp. 31–34. URL: https://www.volgmed.ru/uploads/journals/articles/1293119124-bulletin-2010-4-815.pdf Seredin P., Goloshchapov D., Prutskij T., Ippolitov Y. Phase Transformations in a Human Tooth Tissue at the Initial Stage of Caries. PLoS ONE, 2015, v. 10(4), pp. 1–11. https://doi.org/10.1371/journal.pone.0124008 Seredin P. V., Goloshchapov D. L., Prutskij T., Ippolitov Yu. A. A Simultaneous Analysis of Microregions of Carious Dentin by the Methods of Laser- Induced Fluorescence and Raman Spectromicroscopy. Optics and Spectroscopy, 2018, v. 125(5), pp. 803–809. https://doi.org/10.1134/S0030400X18110267 Seredin P. V., Goloshchapov D. L., Prutskij T., Ippolitov Yu. A. Fabrication and characterisation of composites materials similar optically and in composition to native dental tissues. Results in Physics, 2017, v. 7, pp. 1086–1094. https://doi.org/10.1016/j.rinp.2017.02.025

Introduction: It was reported that the complex, formed between acylated insulin and human serum albumin (HSA), enters an essentially inactive albumin-bound depot, leading to a dramatically decreased potency. Objectives: This study was performed to develop a more potent once-weekly insulin analog GZR4 and investigate its molecular and pharmacological properties. Methods: In vitro assays were employed to characterize the biological attributes of GZR4 through its interactions with HSA and insulin receptor (IR), intracellular signaling, and cellular metabolic responses. In vivo efficacy was evaluated in T1DM STZ treated rats and db/db mice, with Icodec (once-weekly insulin under development) as positive control. Results: GZR4 was designed by introducing C22 fatty acid to B29 lysine of insulin backbone (A14E, B16H, B25H, desB30 human insulin) through 12×OEG linker. GZR4 displayed 2-fold increase in HSA binding, while 1.5-fold decrease in IR-A binding, 2.5-fold decrease in IR-B binding compared with insulin Icodec. In the presence of HSA, a sandwich binding model showed GZR4 retained IR binding response with 10.2 RU while Icodec essentially displayed no binding, IR phosphorylation activity relative to human insulin was 0.233%±0.012% and 0.034%±0.002% for GZR4 and Icodec respectively. In adipocytes, GZR4 stimulated lipogenesis in a similar dose-dependent manner as human insulin. HbA1c-lowering capability of GZR4 was 3 times higher than that of Icodec in TIDM STZ treated rats and db/db mice. Conclusions: Current studies demonstrate that the length of the OEG linker between insulin and fatty acid plays an essential role on the potency of the acylated insulins. In the presence of HSA, GZR4 retains partially in vitro bioactivity while Icodec entered an essentially inactive state. Accordingly, GZR4 showed higher in vivo hypoglycemia efficacy than Icodec. Pharmacological evaluation revealed that GZR4 has the potential to be a novel once-weekly basal insulin with lower dosing compared to Icodec. Disclosure W. Xing: None. W. Chen: None. Y. Zhang: None. J. Gao: None. A. He: None. J. Zhang: None. Y. Deng: None. F. Xue: None. Y. Wang: None. H. Fu: None. R. Zhang: None. J. Huang: None. Z. Gan: None.

Ever since the curriculum reform was launched, 'Reading to Learn' has been one of the four key tasks initiated. The result shown in Progress in International Reading Literacy Study (PIRLS,2011) reflected that the reading ability of Hong Kong Primary students is among the best in the world, whereas their reading motivation ranking the last. Researchers also found in the Programme for International Student Assessment (PISA, 2009) conducted among secondary students that their metacognitive level is the lowest among all the secondary students in South-east Asian districts. It reflected that Hong Kong students lack self-regulation and comprehension monitoring awareness in reading. This dissertation is written in support of an action research and a case study. It aims to discuss the impact on the implementation of teaching of reading strategies on four different primary students, who are of diverse ability on comprehension. In the action research, the researcher tries to enhance students' comprehension monitoring awareness through introducing the K-W-L Chart and Directed Reading and Thinking Activity. In the case study, the researcher makes use of think aloud activities and student interviews to collect and analyze the qualitative data obtained. Together with the quantitative analysis, the researcher studies the reading strategies used among the four selected primary 4 students as well as their understanding toward reading strategies before and after they received the teaching in the process. The research result reflects that teaching reading strategies has a significant effect on enhancing student's reading comprehension monitoring awareness among students, especially the lower ability students. Furthermore, this research makes a few practical suggestions on how to enhance students' reading comprehension awareness in daily teaching. 自課程改革(以下簡稱「課改」)以來，「從閱讀中學習」一直為課改四大關鍵項目之一。「全球學生閱讀能力進展研究(PIRLS，2011)」的結果反映本港小學生的閱讀能力冠絕全球，閱讀動機卻在全球榜尾的奇怪現象；而以中學生為對象的「學生基礎素養能力計劃(PISA，2009)」亦發現本港學生的後設認知能力水平為全東南亞地區最差，反映本港學生在閱讀方面缺乏自我調整和閱讀監控的意識。 本論文旨在以行動研究(action research)及個案研究(case study)方式，探討閱讀策略教學對促進四位小學四年級不同能力學生的閱讀理解監控知覺的影響。在行動研究方面，研究員通過教授自我檢測圖及引領思維閱讀策略，促進學生的理解監控知覺。在個案研究方面，通過放聲思考(think aloud)活動及學生訪談，搜集及分析質性數據，並結合量性分析，探討本港某小學四位四年級學生於接受教學前後，在閱讀過程中運用閱讀策略的情況，以及他們對閱讀策略的認識。研究結果反映，閱讀策略教學對促進學生的閱讀理解監控知覺對於閱讀能力較弱的學生，有明顯的影響。此外，本研究就如何在日常教學中教授閱讀策略，以提升學生的閱讀理解監控知覺方面提出一些建議。
published_or_final_version
Education
Master
Master of Education