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Shen, Li

Publications and source records attributed to Shen, Li.

8 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Integration of evidence across human and model organism studies: A meeting report

The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting's objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and 'omics data across human and model organisms to achieve deeper mechanistic insight into SUDs. Specific topics were to (a) evaluate the current state of substance use genetics and genomics research and fundamental gaps, (b) identify opportunities and challenges of integration and sharing across species and data types, (c) identify current tools and resources for integration of genetic, epigenetic, and phenotypic data, (d) discuss steps and impediment related to data integration, and (e) outline future steps to support more effective collaboration—particularly between animal model research communities and human genetics and clinical research teams. This review summarizes key facets of this catalytic discussion with a focus on new opportunities and gaps in resources and knowledge on SUDs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Polar surface structure of oxide nanocrystals revealed with solid-state NMR spectroscopy

Compared to nanomaterials exposing nonpolar facets, polar-faceted nanocrystals often exhibit unexpected and interesting properties. The electrostatic instability arising from the intrinsic dipole moments of polar facets, however, leads to different surface configurations in many cases, making it challenging to extract detailed structural information and develop structure-property relations. The widely used electron microscopy techniques are limited because the volumes sampled may not be representative, and they provide little chemical bonding information with low contrast of light elements. With ceria nanocubes exposing (100) facets as an example, here we show that the polar surface structure of oxide nanocrystals can be investigated by applying 17 O and 1 H solid-state NMR spectroscopy and dynamic nuclear polarization, combined with DFT calculations. Both CeO 4 -termination reconstructions and hydroxyls are present for surface polarity compensation and their concentrations can be quantified. These results open up new possibilities for investigating the structure and properties of oxide nanostructures with polar facets.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

High-quality mesoporous graphene particles as high-energy and fast-charging anodes for lithium-ion batteries

The application of graphene for electrochemical energy storage has received tremendous attention; however, challenges remain in synthesis and other aspects. Here we report the synthesis of high-quality, nitrogen-doped, mesoporous graphene particles through chemical vapor deposition with magnesium-oxide particles as the catalyst and template. Such particles possess excellent structural and electrochemical stability, electronic and ionic conductivity, enabling their use as high-performance anodes with high reversible capacity, outstanding rate performance (e.g., 1,138 mA h g -1 at 0.2 C or 440 mA h g -1 at 60 C with a mass loading of 1 mg cm -2 ), and excellent cycling stability (e.g., >99% capacity retention for 500 cycles at 2 C with a mass loading of 1 mg cm -2 ). Interestingly, thick electrodes could be fabricated with high areal capacity and current density (e.g., 6.1 mA h cm -2 at 0.9 mA cm -2 ), providing an intriguing class of materials for lithium-ion batteries with high energy and power performance.

25 ENERGY STORAGE↗
DOE OSTI2019

Effect of Niobium on the Secondary Precipitates and Tempering Resistance of Spray-Formed M3:2 High-Speed Steel

The precipitation of secondary carbides in spray-formed M3:2 high-speed steels with or without 2% niobium (Nb) addition during overtempering at 600 °C was characterized, and the carbides were identified in detail using transmission electron microscopy. Strengthening in the peak-hardened state is due to coherent precipitates of types MC and M{sub 2}C. During overtempering, the hardness of M3:2 steel greatly decreases due to M{sub 2}C coarsening with the precipitation of M{sub 3}C carbide, whereas the very fine and dense nature of the M{sub 2}C precipitates is responsible for the remarkable long-time strength exhibited by the Nb-containing steel. The MC precipitates, however, are fairly stable. The addition of Nb results in substantial dissolution of Mo and Cr into the matrix prior to tempering, which refines the secondary M{sub 2}C precipitate dispersion and delays overaging reactions; therefore, superior tempering resistance can be obtained.

36 MATERIALS SCIENCE↗
DOE OSTI2018

PAG1 promotes the inherent radioresistance of laryngeal cancer cells via activation of STAT3

Highlights: • PAG1 is overexpressed in laryngeal cancer. • PAG1 promotes the inherent radioresistance of laryngeal cancer cells. • PAG1 targets and regulates the expression of p-STAT3. • PAG1-integrin β1 complex is involved in the activation of STAT3. Phosphoprotein associated with glycosphingolipid-enriched microdomains 1(PAG1) is a ubiquitous protein that is essential for the development and progression of various malignancies. A previous study in our laboratory confirmed that PAG1 plays an important role in modulating the inherent radioresistance of laryngeal cancer cells, but the underlying mechanisms are still poorly defined. In this study, we found that PAG1 was significantly increased in laryngeal cancer tissues compared to adjacent non-tumor tissues (P < 0.05). The expression of PAG1 was positively correlated with lymph node metastasis (P < 0.05) and TNM stage (P < 0.05). High expression of PAG1 also predicted a poor prognosis in patients with laryngeal cancer. Moreover, gain-of-function and loss-of-function studies showed that PAG1 overexpression was able to promote growth, increase migration and invasion, and enhance inherent radioresistance of laryngeal cancer cells. Mechanistic investigations revealed that the activation of STAT3 was required for PAG1-mediated inherent radioresistance of laryngeal cancer. Inhibition of STAT3 activity with a chemical inhibitor sensitized radioresistant cells to radiation. Importantly, PAG1-integrin β1 complex was involved in the regulation of STAT3 activation. In addition, downregulation of PAG1 could suppress tumor growth and reverse inherent radioresistance in the nude mouse xenograft model. Taken together, these results suggested that PAG1 conferred inherent radioresistance by activating STAT3, which provided a novel therapeutic strategy for laryngeal cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Altered O-glycosylation is associated with inherent radioresistance and malignancy of human laryngeal carcinoma

Highlights: • O-glycosylation contributes to laryngeal carcinoma inherent radioresistance. • O-glycosylation regulates laryngeal carcinoma cell migration and invasion. • O-glycosylation is associated with tumor progression and poor prognosis. • C1GALT1 modifies the O-glycans on integrin β1 and regulates its activity. Radioresistance (inherent or acquired) remains a major obstacle affecting the clinical outcome of radiotherapy for laryngeal carcinoma. Results from our laboratory and other groups suggest that aberrant glycosylation contributes to cancer acquired radioresistance. However, the role of glycosylation in inherent radioresistance of laryngeal carcinoma has not been fully uncovered. In this study, we investigated the glycan profiling of the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2 min) cell lines using lectin microarray analysis. The results revealed that the radioresistant cell line Hep-2max presented higher core 1-type O-glycans than the sensitive one. Further analysis of the O-glycan regulation by benzyl-α-GalNAc application in Hep-2max cells showed partial inhibition of the O-glycan biosynthesis and increased radiosensitivity. In addition, core 1 β1, 3-galactosyltransferase (C1GALT1) overexpression in Hep-2 min cells enhanced cell migration, invasion, and radioresistance. Conversely, knockdown of C1GALT1 in Hep-2max cells was able to suppress these malignant phenotypes. Moreover, mechanistic investigations showed that C1GALT1 modified the O-glycans on integrin β1 and regulated its activity. The glycosylation-mediated radioresistance was further inhibited by anti-integrin β1 blocking antibody. Importantly, we also observed that core 1-type O-glycans expression was correlated with advanced tumor stage, metastasis, and poor survival of laryngeal carcinoma patients. These findings suggest that altered O-glycosylation can lead to the inherent radioresistance and progression, and therefore may be important for enhancing the efficacy of radiotherapy in laryngeal carcinoma.

60 APPLIED LIFE SCIENCES↗