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Li, Lili

Publications and source records attributed to Li, Lili.

MIG/CXCL9 exacerbates the progression of metabolic-associated fatty liver disease by disrupting Treg/Th17 balance

CD4{sup +}CD25{sup +} regulatory T (Treg) cells and Th17 cells play important roles in the progression of metabolic-associated fatty liver disease (MAFLD). However, the contribution of monokine induced by interferon-gamma (MIG)/CXCL9 to the Treg/Th17 imbalance in MAFLD is only partially understood. In the present study, we detected increased levels of MIG/CXCL9 and a Treg/Th17 imbalance in the setting of metabolic-associated steatohepatitis (MASH). Recombinant adeno-associated virus-mediated gene transfer and silencing of MIG/CXCL9 expression in mice alleviated MASH and increased the Treg/Th17 ratio. Furthermore, the percentage of Th17 cells, but not Treg cells, differentiated from splenic CD4{sup +} T cells was significantly increased by administration of MIG/CXCL9. MIG/CXCL9 also promoted Th17 cell proliferation, and its effects were dose dependent. Levels of phosphorylated c-Jun N-terminal kinase (JNK) decreased dramatically when MIG/CXCL9 was inhibited in a murine MASH model. In cultured Treg cells, phosphorylated JNK levels decreased dose-dependently in response to MIG/CXCL9 inhibition, but increased in cultured Th17 cells. This effect was blocked in the presence of a JNK inhibitor. These findings underline the fundamental importance of MIG/CXCL9 in maintaining the Treg/Th17 balance in MAFLD and provide the foundations for a novel approach to preventing and treating MAFLD.

60 APPLIED LIFE SCIENCES↗

Catalytic decomposition of methane into hydrogen and high-value carbons: combined experimental and DFT computational study

Thermocatalytic decomposition (TCD) of methane can produce hydrogen and valuable nanocarbon co-products with low to near-zero CO2 emission. In this study, a series of Pd promoted Ni catalysts, prepared with various Ni/Pd ratios on a CNT support, were evaluated for methane TCD performance. Characterization and calculations using density functional theory (DFT) were carried out to elucidate the activity–structure relationship and growth mechanism of carbon nanomaterials. It was found that the methane conversion and stability of the catalysts were highly dependent on the Ni/Pd ratio and reaction temperature. DFT calculations revealed that the diffusion of carbon in the metal sublayer required for CNT growth was more favorable in the Ni–Pd alloy lattice suggesting that the buildup of carbon in the metal alloy sublayer facilitated the formation of CNTs and CNFs. A cyclic reaction–regeneration process for self-sustained TCD was experimentally demonstrated. In each cycle, a portion of the separated CNT product was used to re-synthesize the Ni–Pd/CNT catalyst for use in the next reaction cycle. After five cycles of operation, the CH4 conversion, morphology and crystallinity of the carbon product remained unchanged.

Wang, I-Wen↗

Microwave catalytic reactor for upgrading stranded shale gas to aromatics

Microwave (MW) catalytic processing has been applied to science discovery in a number of research fields. The potential of MW assisted catalysis in direct ethane dehydroaromatization was explored in this study. Under MW irradiation, significant enhancement in ethane conversion to aromatics was achieved at 400 °C which otherwise would take up to 600 °C in a thermally heated fixed-bed reactor. The role of MW irradiation in activating ethane over the catalyst and the reaction mechanism were elucidated. The results showed that MW could possibly induce the formation of dipoles on catalyst surface, facilitating electron shifting and sharing between catalyst and reaction intermediates. Here, this activation process has significantly lowered activation energy, allowing the reaction to proceed under lower bulk temperature with enhanced aromatic yield.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway

The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. -- Highlights: •Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth. •Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy. •ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.

60 APPLIED LIFE SCIENCES↗

PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC.

60 APPLIED LIFE SCIENCES↗

Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer

Our previous study showed that PLCD1 significantly decreases cell proliferation and affects cell cycle progression in breast cancer cells. In the present study, we aimed to investigate its functional and molecular mechanisms, and whether or not can become a new target for gene therapies. We found reduced PLCD1 protein expression in breast tumor tissues compared with paired surgical margin tissues. PLCD1 promoter CpG methylation was detected in 55 of 96 (57%) primary breast tumors, but not in surgical-margin tissues and normal breast tissues. Ectopic expression of PLCD1 inhibited breast tumor cell proliferation in vivo by inducing apoptosis and suppressed tumor cell migration by regulating cytoskeletal reorganization proteins including RhoA and phospho-cofilin. Furthermore, we found that PLCD1 induced p53 accumulation, increased p27 and p21 protein levels, and cleaved PARP. Finally, we constructed an adenoviral vector expressing PLCD1 (AdH5-PLCD1), which exhibited strong cytotoxicity in breast cancer cells. Our findings provide insights into the development of PLCD1 gene therapies for breast cancer and perhaps, other human cancers. - Highlights: • PLCD1 is downregulated via hypermethylation in breast cancer. • PLCD1 suppressed cell migration by regulating cytoskeletal reorganization proteins. • Adenovirus AdHu5-PLCD1 may be a novel therapeutic option for breast cancer.

60 APPLIED LIFE SCIENCES↗

Geometry optimization for micro-pressure sensor considering dynamic interference

Presented is the geometry optimization for piezoresistive absolute micro-pressure sensor. A figure of merit called the performance factor (PF) is defined as a quantitative index to describe the comprehensive performances of a sensor including sensitivity, resonant frequency, and acceleration interference. Three geometries are proposed through introducing islands and sensitive beams into typical flat diaphragm. The stress distributions of sensitive elements are analyzed by finite element method. Multivariate fittings based on ANSYS simulation results are performed to establish the equations about surface stress, deflection, and resonant frequency. Optimization by MATLAB is carried out to determine the dimensions of the geometries. Convex corner undercutting is evaluated. Each PF of the three geometries with the determined dimensions is calculated and compared. Silicon bulk micromachining is utilized to fabricate the prototypes of the sensors. The outputs of the sensors under both static and dynamic conditions are tested. Experimental results demonstrate the rationality of the defined performance factor and reveal that the geometry with quad islands presents the highest PF of 210.947 Hz{sup 1/4}. The favorable overall performances enable the sensor more suitable for altimetry.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗