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Chen, Si

Publications and source records attributed to Chen, Si.

50 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Mechanical Design Progress of the In Situ Nanoprobe Instrument for APS-U

The In Situ Nanoprobe (ISN, 19-ID) beamline will be a new best-in-class long beamline to be constructed as part of the Advanced Photon Source Upgrade (APS-U) project [1, 2]. To achieve long working distance at high spatial resolution, the ISN instrument will be positioned 210 m downstream of the x-ray source, in a dedicated satellite building, currently under construction [3]. The ISN instrument will use a nano-focusing Kirkpatrick-Baez (K-B) mirror system, which will focus hard x-rays to a focal spot as small as 20 nm, with a large working distance of 61 mm. The large working distance provides space for various in situ sample cells for x-ray fluorescence tomography and ptychographic 3D imaging, allows the use of a separate, independent vacuum chambers for the optics and sample, and provides the flexibility to run experiments in vacuum or at ambient pressure. A consequence of the small spot size and large working distance are stringent requirements for high angular stability of the K-B mirrors (5 nrad V-mirror and 16 nrad H-mirror) and high relative stability be-tween focus spot and sample (4 nmRMS). Additional features include fly-scanning up to 2 kg mass, sample plus in situ cell, at 1 mm/s in vertical and/or horizontal directions over an area of 10 mm x 10 mm. Environmental capabili-ties will include heating and cooling, flow of fluids and applied fields, as required for electrochemistry and flow of gases at high temperature for catalysis. To achieve these capabilities and precise requirements we have used precision engineering fundamentals to guide the design process.

Kearney, Steven P.↗
DOE OSTI2021

Zero-Valent Palladium Single-Atoms Catalysts Confined in Black Phosphorus for Efficient Semi-Hydrogenation

Single-atom catalysts (SACs) represent a new frontier in heterogeneous catalysis due to their remarkable catalytic properties and maximized atomic utilization. However, single atoms often bond to the support with polarized electron density and thus exhibit a high valence state, limiting their catalytic scopes in many chemical transformations. In this study, it is demonstrated that 2D black phosphorus (BP) acts as giant phosphorus (P) ligand to confine a high density of single atoms (e.g., Pd 1 , Pt 1 ) via atomic layer deposition. Unlike other 2D materials, BP with relatively low electronegativity and buckled structure favors the strong confinement of robust zero-valent palladium SACs in the vacancy site. Metallic Pd 1 /BP SAC shows a highly selective semi-hydrogenation of phenylacetylene toward styrene, distinct from metallic Pd nanoparticles that facilitate the formation of fully hydrogenated products. Density functional theory calculations reveal that Pd atom forms covalent-like bonding with adjacent P atoms, wherein H atoms tend to adsorb, aiding the dissociative adsorption of H 2 . Zero-valent Pd in the confined space favors a larger energy gain for the synthesis of partially hydrogenated product over the fully hydrogenated one. This work provides a new route toward the synthesis of zero-valent SACs on BP for organic transformations.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Development of Fe 3 O 4 core–TiO 2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization

Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe 3 O 4 core-TiO 2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe 3 O 4 core-TiO 2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe 3 O4@TiO 2 as potential radiosensitizers for neuroblastoma in vitro. The uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs. The intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization – use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2021

Single-cell visualization and quantification of trace metals in Chlamydomonas lysosome-related organelles

Significance Transition metals are of crucial importance for primary productivity; their scarcity limits crop yield in agriculture and carbon sequestration on a global scale. Copper (Cu), iron (Fe), and manganese (Mn) are among the most important trace elements that enable the redox chemistry in oxygenic photosynthesis. The single-celled, eukaryotic green alga Chlamydomonas reinhardtii is a choice experimental system for studying trace metal homeostasis in the context of phototrophy, offering all the advantages of a classical microbial system with a well-characterized photosystem and trace metal metabolism machinery of relevance to plants. This project identifies and differentiates different trace metal storage sites in Chlamydomonas and uncovers the dynamics of trace metal storage and mobilization in situations of fluctuating resources.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma

Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference–based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial ( NCT03020017 ) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment–related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129–treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

XRFtomo

Based on [1], XRFtomo brings together a variety of image processing tools used for preparing, processing and reconstructing 3D renditions of samples imaged using a synchrotron-based x-ray fluorescence (XRF) microprobe or nanoprobe at the Advanced Photon Source (APS). This software bridges the gap between data acquisition and visualization by providing tools to adjust for misalignment in the imaging process and tools for running reconstructions[2], all with the use of a GUI or command line. XRFtomo accepts .h5 files processed through MAPS[3] and it outputs reconstructed cross-sections, projections, sinograms, metadata, and a configuration file with last-used parameters for rapid processing the next time the program is launched. These images serve as inputs for other 3D visualization software for generating volumetric renderings and animations.

Marin, Fabrico↗
DOE OSTI2020

Fracture toughness of zirconia with a nanometer size notch fabricated using focused ion beam milling

Zirconia with 3 mol% yttria (3Y-TZP) has been used for dental crowns and bridges due to its excellent mechanical behavior. Performing fracture toughness testing on this nanograin material, however, can be a challenge. For reliable results, fracture toughness testing requires an extremely sharp notch in the test specimen that closely approximates a very sharp crack. This study was to investigate an alternative method to produce nanometer-sized notches, which are less than the average grain size of 3Y-TZP, during the preparation of single-edge V-notched beam specimens and report the resulting fracture toughness value. We present a method using focused ion beam (FIB) milling to fabricate nanometer-sized notches in 3Y-TZP. The notch tip is <100 nm wide, which is smaller than the grain size, and is consistent throughout the thickness of the specimen. The FIB-notched specimens show a much reduced average fracture toughness of 5.64 ± 1.14 MPa√m compared to 8.90 ± 0.23 MPa√m for the specimens without FIB-notches. The FIB-milling did not appear to create any monoclinic phase prior to fracture toughness testing. Fractures originated at the FIB-notches, and the notch size can be readily identified post-mortem using a microscope. A considerable amount of tetragonal-to-monoclinic phase transformation was observed throughout the fracture surfaces. FIB milling provides an alternative method to fabricate nanometer-sized notches that are smaller than the grain size of tetragonal zirconia polycrystal. The fracture toughness determined using FIB-notches was ~5.64 MPa√m, smaller than the specimens with V-notches fabricated using saw blades.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Lipids status and copper in a single astrocyte of the rat model for amyotrophic lateral sclerosis: Correlative synchrotron-based X-ray and infrared imaging

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, causing death of motor neurons controlling voluntary muscles. The pathological mechanisms of the disease are only partially understood. The hSOD1-G93A ALS rat model is characterized by an overexpression of human mutated SOD1, causing increased vulnerability by forming intracellular protein aggregates, inducing excitotoxicity, affecting oxidative balance and disturbing axonal transport. In this study we followed the bio-macromolecular organic composition and compartmentalization together with trace metal distribution in situ in single astrocytes from the ALS rat model and compared them to the control astrocytes from nontransgenic littermates by simultaneous use of two synchrotron radiation-based methods: Fourier transform infrared microspectroscopy (SRFTIR) and hard X-ray fluorescence microscopy (XRF). Here we show that ALS cells contained more Cu, which colocalized with total lipids, increased carbonyl groups and oxidized lipids, thus implying direct involvement of Cu in oxidative stress of lipidic components without direct connection to protein aggregation in situ.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Development and Application of TK6-derived Cells Expressing Human Cytochrome P450s for Genotoxicity Testing

Abstract Metabolism plays a key role in chemical genotoxicity; however, most mammalian cells used for in vitro genotoxicity testing lack effective metabolizing enzymes. We recently developed a battery of TK6-derived cell lines that individually overexpress 1 of 8 cytochrome P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, and 3A4) using a lentiviral expression system. The increased expression and metabolic function of each individual CYP in each established cell line were confirmed using real-time PCR, Western blotting, and mass spectrometry analysis; the parental TK6 cells and empty vector (EV) transduced cells had negligible CYP levels. Subsequently, we evaluated these cell lines using 2 prototypical polyaromatic hydrocarbon mutagens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P), that require metabolic activation to exert their genotoxicity. DMBA-induced cytotoxicity, phosphorylation of histone H2A.X, and micronucleus formation were significantly increased in TK6 cells with CYP1A1, 1B1, 2B6, and 2C19 expression as compared with EV controls. B[a]P significantly increased cytotoxicity, DNA damage, and chromosomal damage in TK6 cells overexpressing CYP1A1 and 1B1 when compared with EV controls. B[a]P also induced micronucleus formation in TK6 cells expressing CYP1A2. These results suggest that our CYP-expressing TK6 cell system can be used to detect the genotoxicity of compounds requiring metabolic transformation.

Li, Xilin↗