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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Application of iPSCs derived pancreatic β-like cells using pancreatic bio-scaffold

This study aimed toengineer a pancreatic tissue. Intact rat pancreases were successfully decellularized, and were reseeded with human-induced pluripotent stem cells using different 2D and 3D culture growth factors. The differentiation process was assessed for the presence of a pancreas-like tissue. The histology and SEM analysis revealed cell attachment in all samples, except for the Exp4, and the Flow-cytometry provided 87% viability for the differentiated cells. In Exp1, PDX1 with the positive expression of 2.87±0.06 was dramatically higher than Exp2 with a 2.44±0.06 reaction. NGN3-reactions were 8±0.1 and 6.6±0.2 in Exp1 and Exp2 at P < 0.05, respectively. C-peptide with the expression of 7.5±0.7 in Exp3 was almost equal to that in Exp1 and Exp2. Glucagon (5.1±1) and PDX1 (3.2±0.82) in Exp3 indicated no significant difference. The significant upregulations of pancreatic endocrine markers (PDX1 and NGN3), and the cell-specific glucose transporter (GLUT2) were observed in the differentiated IPCs in the 3D culture of Exp2 after 21 days. The highest insulin and C-peptide concentrations were observed in Exp2. In Exp3, insulin secretion in response to high glucose and 10 mM arginine was 42.43 ±6.34 μU/ml. A decellularized pancreas in the presence of hiPSCs and growth factors could be efficiently used as a natural scaffold.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy

Highlights: • The expression of USP12 is increased in Ang II-induced cardiac hypertrophy in vitro and in vivo. • USP12 aggravates Ang II-induced cardiomyocyte hypertrophy via upregulating METTL3. • USP12 promoted METTL3 expression via modulating p300. • USP12 suppresses the ubiquitination of p300 to block its degradation. Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N{sup 6}-methyladenosine (m{sup 6}A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

EP300/CBP is crucial for cAMP-PKA pathway to alleviate podocyte dedifferentiation via targeting Notch3 signaling

Podocyte injury is the hallmark of proteinuric glomerular diseases. Notch3 is neo-activated simultaneously in damaged podocytes and podocyte's progenitor cells of FSGS, indicating a unique role of Notch3. We previously showed that activation of cAMP-PKA pathway alleviated podocyte injury possibly via inhibiting Notch3 expression. However, the mechanisms are unknown. In the present study, Notch3 signaling was significantly activated in ADR-induced podocytes in vitro and in PAN nephrosis rats and patients with idiopathic FSGS in vivo, concomitantly with podocyte dedifferentiation. In cultured podocytes, pCPT-cAMP, a selective cAMP-PKA activator, dramatically blocked ADR-induced activation of Notch3 signaling as well as inhibition of cAMP-PKA pathway, thus alleviating the decreased cell viability and podocyte dedifferentiation. Bioinformatics analysis revealed EP300/CBP, a transcriptional co-activator, as a central hub for the crosstalk between these two signaling pathways. Additionally, CREB/KLF15 in cAMP-PKA pathway competed with RBP-J the major transcriptional factor of Notch3 signaling for binding to EP300/CBP. EP300/CBP siRNA significantly inhibited these two signaling transduction pathways and disrupted the interactions between the above major transcriptional factors. These data indicate a crucial role of EP300/CBP in regulating the crosstalk between cAMP-PKA pathway and Notch3 signaling and modulating the phenotypic change of podocytes, and enrich the reno-protective mechanisms of cAMP-PKA pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

MiR-125b enhances autophagic flux to improve septic cardiomyopathy via targeting STAT3/HMGB1

We explore the role of miR-125b in septic cardiomyopathy, focusing on miR-125b/STAT3/HMGB1 axis. CLP mouse model and LPS-stimulated primary rat cardiomyocytes (CMs) and H9C2 cell were used as in vivo and in vitro models of septic cardiomyopathy, respectively. qRT-PCR and western blot were performed to measure expression levels of miR-125b, STAT3, HMGB1, and autophagy-related proteins. MTT assay was employed to examine LPS toxicity. Dual luciferase activity assay and CHIP were performed to validate interactions of miR-125b/STAT3 and STAT3/HMGB1 promoter. Immunostaining was used to assess the level of autophagic flux. ROS level was measured by fluorescence assay. Heart functions were examined via intracoronary Doppler ultrasound. miR-125b was diminished while STAT3 and HMGB1 were elevated in the heart tissue following CLP surgery and in LPS-treated H9C2 cells. LPS treatment up-regulated ROS generation and suppressed autophagic flux. Overexpression of miR-125b mimics or knockdown of STAT3 or HMGB1 alleviated LPS-induced hindrance of autophagic flux and ROS production. miR-125b directly targeted STAT3 mRNA and STAT3 bound with HMGB1 promoter. Overexpression of miR-125b mitigated myocardial dysfunction induced by CLP in vivo. Hyperactivation of STAT3/HMGB1 caused by reduced miR-125b contributes to ROS generation and the hindrance of autophagic flux during septic cardiomyopathy, leading to myocardial dysfunction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Decellularized ECM derived from normal bone involved in the viability and chemo-sensitivity in multiple myeloma cells

Multiple myeloma (MM) is an incurable plasma cell malignancy. The progression of MM is closely related to the bone microenvironment. Bone matrix proteins are remodeled and manipulated to govern cancer growth during the process of MM. However the role of normal bone extracellular matrix in MM is still unclear. In this study the decellularized extracellular matrix derived from normal SD rats’ skulls (N-dECM) was prepared by decellularization technology. The CCK 8 assay and the dead-live cell kit assay were used to determine the viability of MM cells and the sensitivity to bortezomib. The Realtime PCR and Western blot assay were used to assay the mRNA and protein related to MM. Under the treatment of N-dECM, we found that the viability of MM cells was inhibited and the sensitivity of MM cells to bortezomib was increased. Additionally, the expression levels of APRIL and TACI, which participated in the progression of MM, were significantly decreased in MM cells. It suggested that N-dECM might inhibit the development of MM via APRIL-TACI axis, and our study may provide a novel and potential biomaterial for MM therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

miR-126 regulates angiogenesis in myocardial ischemia by targeting HIF-1α

Promoting angiogenesis by targeting various angiogenic regulators has emerged as a new treatment strategy for myocardial ischemia (MI). MicroRNA-126 (miR-126) has been identified as the main regulator of compensatory angiogenesis; however, its role in MI is unclear. A rat MI model and an EA. hy926 endothelial cell hypoxia model were constructed and it was found that miR-126 was highly expressed in both models. The knockdown of HIF-1α expression in EA. hy926 cells in turn downregulated VEGF and CD34 expression and consequently inhibited angiogenesis. MiR-126 inhibitor inhibited EA. hy926 cell migration and tube formation as well as downregulated VEGF and CD34 expression, and these were reversed by transfection of miR-126 mimics. Rescue tests using miR-126 and HIF-1α demonstrated that miR-126-mediated regulation of angiogenesis was dependent on HIF-1α. In summary, miR-126 regulates the occurrence and progression of angiogenesis during MI via HIF-1α and may be a potential new therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model

Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions. We aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation. A sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model k-values in experimental groups: sham control (SC, n = 5, 0.0 mA / 0 Hz), stimulation level 1 (SL1, n = 5, 3.4 mA / 50 Hz, and k = 2.57), and stimulation level 2 (SL2, n = 5, 6.8 mA / 100 Hz, and k = 3.17). The stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of +4 % / – 309 % (SL1/SL2) in phase retardation and –79 % / – 148 % in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a +1 % / – 36 % difference in myelin pixel counts and –13 % / + 29 % difference in axon pixel counts, and an overall increase in cell nuclei pixel count of +20 % / + 35 % . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis. The poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Heavy Ion Minibeam Therapy: Side Effects in Normal Brain

The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium-7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300-micron width and 1-mm center-to-center spacing within a circular array. We followed animals for 6 months after treatment and utilized behavioral testing and immunohistochemical studies to investigate the resulting cognitive impairment and chronic pathologic changes. We found both solid-beam therapy and minibeam therapy to result in cognitive impairment compared with sham controls, with no apparent reduction in neurotoxicity using heavy ion minibeams instead of solid beams under the conditions of this study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Identification of an Attenuated Substrain of Francisella tularensis SCHU S4 by Phenotypic and Genotypic Analyses

Pneumonic tularemia is a highly debilitating and potentially fatal disease caused by inhalation of Francisella tularensis. Most of our current understanding of its pathogenesis is based on the highly virulent F. tularensis subsp. tularensis strain SCHU S4. However, multiple sources of SCHU S4 have been maintained and propagated independently over the years, potentially generating genetic variants with altered virulence. In this study, the virulence of four SCHU S4 stocks (NR-10492, NR-28534, NR-643 from BEI Resources and FTS-635 from Battelle Memorial Institute) along with another virulent subsp. tularensis strain, MA00-2987, were assessed in parallel. In the Fischer 344 rat model of pneumonic tularemia, NR-643 and FTS-635 were found to be highly attenuated compared to NR-10492, NR-28534, and MA00-2987. In the NZW rabbit model of pneumonic tularemia, NR-643 caused morbidity but not mortality even at a dose equivalent to 500x the LD 50 for NR-10492. Genetic analyses revealed that NR-10492 and NR-28534 were identical to each other, and nearly identical to the reference SCHU S4 sequence. NR-643 and FTS-635 were identical to each other but were found to have nine regions of difference in the genomic sequence when compared to the published reference SCHU S4 sequence. Given the genetic differences and decreased virulence, NR-643/FTS-635 should be clearly designated as a separate SCHU S4 substrain and no longer utilized in efficacy studies to evaluate potential vaccines and therapeutics against tularemia. View Full-Text

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Boron‐Doped Nano‐Crystalline Coated Carbon Fibers for Phasic Dopamine Sensing

Real time, chronic electrochemical detection of neurotransmitters will provide a positive step in the treatment and understanding of neurological disease. However, current electrodes using carbon fibers (CF) fail to perform chronically. While diamond-based coatings show promise in improving their longevity, achieving a uniform layer of such coatings on CFs is challenging, and the electrodes often lose sensitivity after coating. In this work, a complete and uniform boron-doped nanocrystalline material grown in a diamond reactor (B-NCD) was developed to coat CF microelectrodes for neurochemical sensing. The coating was characterized electrically, optically, mechanically, and chemically. The B-NCD coated CF electrodes were able to detect phasic dopamine at a sensitivity comparable to the most widely used alternatives (uncoated and PEDOT:Nafion coated CFs). During biofouling testing, the B-NCD coated CF electrodes demonstrated better stability than uncoated CFs and comparable performance to PEDOT:Nafion coated CFs. Moreover, B-NCD exhibited no signs of degradation during consecutive FSCV applications, while uncoated and PEDOT:Nafion coated CF electrodes degraded significantly over time. Furthermore, the B-NCD coating supported the survival and development of neurons and astrocytes in vitro, exhibited excellent adhesion and durability during mechanical bending testing, and enabled successful in vivo recording of phasic dopamine release in the rat brain. Overall, B-NCD coated CFs present as an ideal candidate for chronic, flexible neural implantable electrodes for long-term neurochemical monitoring.

carbon fiber↗
DOE OSTI2022

Porous Polymers as Universal Reversal Agents for Heparin Anticoagulants through an Inclusion–Sequestration Mechanism

Heparins are widely used anticoagulants for surgical procedures and extracorporeal therapies. However, all of them have bleeding risks. Protamine sulfate, the only clinically approved antidote for unfractionated heparin (UFH), has adverse effects. Moreover, protamine can only partially neutralize low-molecular-weight heparins (LMWHs) and is not effective for fondaparinux. In this report an inclusion–sequestration strategy for efficient neutralization of heparin anticoagulants by cationic porous supramolecular organic frameworks (SOFs) and porous organic polymers (POPs) is reported. Isothermal titration calorimetric and fluorescence experiments show strong binding affinities of these porous polymers toward heparins, whereas dynamic light scattering and zeta potential analysis confirm that the heparin sequences are adsorbed into the interior of the porous hosts. Activated partial thromboplastin time, anti-FXa, and thromboelastography assays indicate that their neutralization efficacies are higher than or as high as that of protamine for UFH and generally superior to protamine for LMWHs and fondaparinux, which is further confirmed by tail-transection model in mice and ex vivo aPTT or anti-FXa analysis in rats. Acute toxicity evaluations reveal that one of the SOFs displays outstanding biocompatibility. This work suggests that porous polymers can supply safe and rapid reversal of clinically used heparins, as protamine surrogates, providing an improved approach for their neutralization.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Microelectrode Arrays Measure Blocking of Voltage-Gated Calcium Ion Channels on Supported Lipid Bilayers Derived from Primary Neurons

Drug studies targeting neuronal ion channels are crucial to understand neuronal function and develop therapies for neurological diseases. The traditional method to study neuronal ion-channel activities heavily relies on the whole-cell patch clamp as the industry standard. However, this technique is both technically challenging and labour-intensive, while involving the complexity of keeping cells alive with low throughput. Therefore, the shortcomings are limiting the efficiency of ion-channel-related neuroscience research and drug testing. Here, this work reports a new system of integrating neuron membranes with organic microelectrode arrays (OMEAs) for ion-channel-related drug studies. This work demonstrates that the supported lipid bilayers (SLBs) derived from both neuron-like (neuroblastoma) cells and primary neurons are integrated with OMEAs for the first time. The increased expression of voltage-gated calcium (CaV) ion channels on differentiated SH-SY5Y SLBs compared to non-differentiated ones is sensed electrically. Also, dose-response of the CaV ion-channel blocking effect on primary cortical neuronal SLBs from rats is monitored. The dose range causing ion channel blocking is comparable to literature. This system overcomes the major challenges from traditional methods (e.g., patch clamp) and showcases an easy-to-test, rapid, ultra-sensitive, cell-free, and high-throughput platform to monitor dose-dependent ion-channel blocking effects on native neuronal membranes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Transforming layered 2D mats into multiphasic 3D nanofiber scaffolds with tailored gradient features for tissue regeneration

Abstract Multiphasic scaffolds with tailored gradient features hold significant promise for tissue regeneration applications. Herein, this work reports the transformation of two‐dimensional (2D) layered fiber mats into three‐dimensional (3D) multiphasic scaffolds using a ‘solids‐of‐revolution’ inspired gas‐foaming expansion technology. These scaffolds feature precise control over fiber alignment, pore size, and regional structure. Manipulating nanofiber mat layers and Pluronic F127 concentrations allows further customization of pore size and fiber alignment within different scaffold regions. The cellular response to multiphasic scaffolds demonstrates that the number of cells migrated and proliferated onto the scaffolds is mainly dependent on the pore size rather than fiber alignment. In vivo subcutaneous implantation of multiphasic scaffolds to rats reveals substantial cell infiltration, neo tissue formation, collagen deposition, and new vessel formation within scaffolds, greatly surpassing the capabilities of traditional nanofiber mats. Histological examination indicates the importance of optimizing pore size and fiber alignment for the promotion of cell infiltration and tissue regeneration. Overall, these scaffolds have potential applications in tissue modeling, studying tissue‐tissue interactions, interface tissue engineering, and high‐throughput screening for optimized tissue regeneration.

Shahriar, S. M. Shatil↗
DOE OSTI2020

Antihypertensive effect of quinoa protein under simulated gastrointestinal digestion and peptide characterization

Abstract BACKGROUND Quinoa protein is a potential source of bioactive peptides. Although some studies have demonstrated its angiotensin converting enzyme (ACE) inhibitory properties, research into its in vivo effect on blood‐pressure regulation and peptide characterization remains limited. RESULTS Quinoa protein hydrolyzate (QPH) was prepared by simulated gastrointestinal digestion. QPH lowered the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive model rats (SHRs) from 2 h to10 h after oral administration, effectively controlling blood pressure in these SHRs. An in vitro study showed that QPH is capable of inhibiting ACE activity. This was attributed to the activity of a number of low‐molecular‐weight peptides. With relatively high scores predicted by PeptideRanker, three promising bioactive peptides, FHPFPR, NWFPLPR, and NIFRPF, were further studied and their ACE‐inhibition effects were confirmed with IC 50 values of 34.92, 16.77, and 32.40 μM, respectively. A molecular docking study provided insights into the binding of ACE with peptides, and revealed that the presence of specific amino acids in the peptide sequence (Pro, Phe, and Arg at the C‐terminal, and Asn at the N‐terminal) could contribute to the interaction between ACE and peptides. CONCLUSION These results demonstrated the potential of QPH for the management of hypertension, which indicates that it could be a good candidate for inclusion in functional foods to control high blood pressure. © 2020 Society of Chemical Industry

Guo, Huimin↗
DOE OSTI2022

Wogonoside attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis through SOCS1 / P53 / SLC7A11 pathway

Abstract Wogonoside (WG) is a flavonoid chemical component extracted from Scutellaria baicalensis, which exerts therapeutic effects on liver diseases. Ferroptosis, a novel form of programmed cell death, regulates diverse physiological/pathological processes. In this study, we attempted to investigate a novel mechanism by which WG mitigates liver fibrosis by inducing ferroptosis in hepatic stellate cells (HSCs). A CCl 4 ‐induced mouse liver fibrosis model and a rat HSC line were employed for in vivo and in vitro experiments, both treated with WG. Firstly, the levels of the fibrotic markers α‐smooth muscle actin (α‐SMA) and α1(I)collagen (COL1α1) were effectively decreased by WG in CCl 4 ‐induced mice and HSC‐T6 cells. Additionally, mitochondrial condensation and mitochondrial ridge breakage were observed in WG‐treated HSC‐T6 cells. Furthermore, ferroptotic events including depletion of SLC7A11, GPX4 and GSH, and accumulation of iron, ROS and MDA were discovered in WG‐treated HSC‐T6 cells. Intriguingly, these ferroptotic events did not appear in hepatocytes or macrophages. WG‐elicited HSC ferroptosis and ECM reduction were dramatically abrogated by ferrostatin‐1 (Fer‐1), a ferroptosis inhibitor. Importantly, our results confirm that SOCS1/P53/SLC7A11 is a signaling pathway which promotes WG attenuation of liver fibrosis. On the contrary, WG mitigated liver fibrosis and inducted HSC‐T6 cell ferroptosis were hindered by SOCS1 siRNA and pifithrin‐α (PFT‐α). These findings demonstrate that SOCS1/P53/SLC7A11‐mediated HSC ferroptosis is associated with WG alleviating liver fibrosis, which provides a new clue for the treatment of liver fibrosis.

Liu, Guofang↗
DOE OSTI2026

Temporal multi-omic analysis uncovers sex-biased molecular programs underlying skeletal muscle adaptation to endurance training

Background. Exercise training is known to benefit health and reduce disease risk. While adaptations in skeletal muscles are fundamental to many of the health benefits of exercise training, the common and sex-specific molecular regulators that mediate these adaptations remain to be fully elucidated. Methods. To this end, we leveraged skeletal muscle multi-omics data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), where 6 month-old male and female rats endurance trained for 1, 2, 4, or 8 weeks. Our objective was to identify shared and sex-specific multi-omic molecular responses to endurance training in skeletal muscle, and relate them to phenotypic adaptations. Results. We identified largely sexually-conserved transcriptomic and proteomic enrichments in the gastrocnemius, which correlated with skeletal muscle responses from a published exercise study in humans. We uncovered sex-consistent post-translational modifications, including decreased oxidation of MYH2 and deacetylation of the ß-oxidation enzyme HADHA. Pathway enrichment analyses revealed sex-specific remodeling across the acetylome, redox proteome, and phosphoproteome; females decreased mitochondrial protein oxidation and increased mitochondrial cristae proteins, indicative of enhanced redox buffering and mitochondrial efficiency. Despite observed decreases in the oxidation of key mitochondrial proteins, females displayed increases in the oxidation of proteins involved in glucose catabolism relative to males after 8 weeks of training, suggestive of sex-biased subcellular reactive oxygen species generation. Conclusions. This work shows a large portion of the adaptive response to endurance training in skeletal muscle is shared between females and males, while there are distinct and nuanced sex-specific adaptations that are evident, particularly at the level of post-translational regulation.

Many, Gina M.↗
DOE OSTI2020

Synergistic enhancement of nanocellulose foam with dual in situ mineralization and crosslinking reaction

Cellulose nanocrystals (CNCs) foams have recently gained research interests because they are renewable, abundant, biodegradable and exhibit high surface area. However, the application of CNCs-based foams is still challenging, which is attributed to its lack of effective entanglements between the CNCs particles, thus lowering foam properties. In this study, a synergistic enhancement strategy was proposed, based on the in situ mineralization with hydroxyapatite (HAP) layer onto the CNCs surface, followed by a chemical crosslinking reaction. The physical and chemical structures of the composites were analyzed with SEM, STEM, XRD, FTIR, and TGA. By controlling the amount of coated HAP and the crosslinker, it is possible to manufacture a series of CNCs-based foams that are lightweight (50–75 mg/cm 3 ), highly porous (~90%) with high water absorption (>1300%) and outstanding mechanical strength properties (as high as 1.37 MPa). Moreover, our study further indicated that these CNCs/HAP materials could increase the proliferation of rat osteoblast cells. The method developed in this study presents a novel approach to design improved networked CNCs foam, which has the potential to be used in thermal-retardant material, wastewater treatment, tissue engineering, and personal care applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1– 13 C]pyruvate in vivo

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however, in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1– 13 C]pyruvate. Biocompatible formulations of hyperpolarized [1– 13 C]pyruvate in, both, methanol-water, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as a minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe and scalable molecular imaging.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗