5 results on '"Liu, Tianyi"'
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2. Power Comparison of Some Goodness-of-fit Tests
- Author
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Liu, Tianyi, primary
- Full Text
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3. Studies of Sustainable Polymers: Novel Lignins to Reprocessable Polymers
- Author
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Liu, Tianyi
- Subjects
- Lignin, Monolignol, Degradation, Quartz Crystal Microbalance with Dissipation Monitoring, Vitrimer
- Abstract
This dissertation includes two research topics. This first topic focuses on fundamental studies of monolignols and lignin, including polymerization and degradation. The second part reports a polymeric material that was crosslinked but can be reprocessed. In order to understand lignin from a molecular level and promote biopolymer conversion, we investigated the dehydrogenative copolymerization and degradation of two monolignols: caffeyl (C) alcohol and p-coumaryl (H) alcohol. The copolymerization and degradation were monitored by a quartz crystal microbalance with dissipation (QCM-D). Atomic force microscopy (AFM) was applied to investigate the topologies of the copolymer and degraded films. Horseradish peroxidase (HRP) was used as the enzyme for the dehydrogenative polymerization of monolignols and chelator-mediated Fenton chemistry was used to degrade the lignin. With constant monolignol concentration, we found that as the fraction of H in the polymerization feed increased, the amount of lignin formed increased, and the films became more rigid. For the degradation process of the resultant lignins, the presence of more C-monolignol during polymerization facilitated greater degradation. This work demonstrated the chemical factors that influenced the physical properties of lignin and lignin degradation, which could impact biofuel production. We further investigated the surface-initiated dehydrogenative polymerization of a new monolignol 5-hydroxyconiferyl (5H) alcohol using a QCM-D. HRP was immobilized on gold sensors. Various experimental conditions were studied. The dehydrogenative polymerization of 5H-monolignol was influenced by the concentration of monolignols and temperature, but was not affected by the hydrogen peroxide concentration, which was different from other monolignols. We also compared the polymerization kinetics of 5H-monolignol and the topology of the resulting lignin thin films with other monolignols. Furthermore, we utilized enzymatic and chemical degradation methods to treat the 5H-lignin. The 5H-lignin film was degraded thoroughly via a chelator-mediated Fenton reaction. This study provided a comprehensive understanding of 5H-monolignol polymerization and degradation and could be used as a reference for the exploration of the applications of the 5H-monolignol. In this dissertation, a separate study involved a vitrimer. It was a crosslinked polymer, but could be reprocessed and reshaped. The new vitrimer was based on poly (methyl methacrylate-co-hydroxymethyl methacrylate). Aromatic disulfides that underwent a dynamic exchange reaction were incorporated as crosslinkers. The structure of the material was identified by proton nuclear magnetic resonance spectroscopy (1H NMR) and Fourier transform infrared spectroscopy (FTIR). Thermal properties and mechanical properties were studied through thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), and Instron tests. Furthermore, the chemical resistance was explored. Notably, that new material exhibited comparable mechanical performance for three cycles when reprocessed via a hot press to reprocess.
- Published
- 2022
4. BRAF Inhibitors Stimulate CAFs to Drive Drug Resistance in Melanoma
- Author
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Liu, Tianyi
- Subjects
- Pharmaceuticals, cancer-associated fibroblast, melanoma, BRAF inhibitor, drug resistance, beta-catenin, periostin
- Abstract
Although the groundbreaking discovery of RAF and MEK inhibitors has revolutionized targeted therapy for the treatment of advanced melanoma, a high percentage of patients still die from metastasis despite the initial positive responses to targeted therapy drugs. Both tumor progression and the development of therapeutic resistance are strongly modulated by stromal cells that reside in the tumor microenvironment (TME). The TME is composed of noncancer stromal cells, including endothelial cells, immune cells, and cancer-associated fibroblasts (CAFs), and the noncellular extracellular matrix (ECM). During the past decade, there is a great expansion in research on CAFs, which is one of the most abundant and active stromal cell types to aid the creation of a desmoplastic tumor niche. CAFs have multifaceted roles in regulating tumor progression, including synthesis and remodeling of the ECM and production of growth factors, modulating anti-tumor immune response, and influencing angiogenesis, tumor mechanics, drug access and therapy responses. Although TME-mediated drug resistance mechanism has been extensively studied in the past, it is still not clear how therapy-induced pressure would act on the genetically stable stromal cells and how these cells could add in the occurrence of drug resistance. Here, we show that the number of intratumoral CAFs increases in BRAF inhibitors (BRAFi)/MEK inhibitors (MEKi)-treated melanoma stroma. CAFs also exhibit increased amounts of nuclear ß-catenin under BRAFi/MEKi therapy. ß-catenin has critical roles in both the Wnt/ ß-catenin signaling pathway and cell-cell adhesion. Wnt/ß-catenin signaling is one of the key signaling pathways that are deregulated not only in a variety of human cancer cells, and also in fibroblasts. Aberrant activation of ß-catenin signaling in fibroblasts has been demonstrated to lead to diseases, such as skin fibrosis. Our results suggest that CAFs, which possess the wild-type BRAF gene, could be paradoxically activated via BRAF and CRAF dimerization, which triggers the MEK/ERK signaling pathway and finally leads to increased nuclear ß-catenin expression in CAFs. Further studies show that BRAFi not only leads to increased ß-catenin nuclear accumulation in CAFs and stimulates their biological properties, suggesting BRAFi induces a new resistant phenotype in CAFs. In both in vitro and in vivo models, depleting ß-catenin in CAFs abolishes their ability to elicit melanoma cell growth and drug resistance. RNA-Seq data reveals that ß-catenin is a major regulator of CAF phenotype. We identify matricellular protein periostin (POSTN) as a downstream effector of ß-catenin. In melanoma, periostin is uniquely expressed in CAFs, and BRAFi can specifically upregulate periostin production in CAFs but not in melanoma cells. Recombinant periostin contributes to melanoma cell resistance to BRAFi/MEKi and can compensate for the loss of ß-catenin in CAFs. Additionally, our study reveals that periostin activates PI3K/AKT signaling in melanoma cells, which reactivates the ERK signaling pathway blocked by BRAFi and MEKi. In summary, our data provide a mechanistic insight into the functional reprogramming of CAFs by BRAFi, which is mediated by Wnt-independent nuclear ß-catenin transcriptional activity and periostin as an important downstream effector in conferring BRAFi/MEKi resistance in melanoma.
- Published
- 2021
5. A STRETCHABLE HYDROGEL VIA GRAFTING ALKANE AND POLYSYRENE ONTO ISOBAM
- Author
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Liu, Tianyi
- Subjects
- Polymers
- Abstract
Hydrogel is a polymeric material that has the ability to absorb and retain a large amount of water within the space between its polymeric chains The flexibility of synthetic hydrogels is very similar to natural tissue, and the water it consists makes it biocompatible, so it can be used in many bio-applications, such as tissue engineering , drug delivery , and wound dressing. However, the poor mechanical behaviors of hydrogels often limit its applications, because of their lack of energy dissipation mechanism. In this study, hydrogels with high toughness were developed by introducing hydrophobic interactions to dissipate energy. Grafting copolymer was synthesized by ISOBAM, polystyrene and alkane chains to form the hydrogel. ISOBAM was used as the backbone; polystyrene was used for permanent crosslink; alkane chains were used to form hydrophobic integrations. Tensile mechanical properties of the hydrogel with different amount of alkane chains and different water content were measured. In addition, rheology test was adapted to study the structure of the hydrogel.
- Published
- 2017
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