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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 1,027 records · Page 57
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

The transformation of U(VI) and V(V) in carnotite group minerals during dissimilatory respiration by a metal reducing bacterium

Recent results from laboratory and field studies support that dissimilatory metal reducing (DMR) bacteria influence the fate and transport of uranium in anaerobic subsurface environments. To date, most research efforts have focused on the reduction of soluble U(VI) by DMR bacteria to form insoluble uraninite (UO 2 ). Subsurface environments harbor, however, large reservoirs of U(VI) in solid or mineral form. Uranium that is structure-bound in minerals is expected to be more refractory to microbial reduction than soluble U, based on analogy with Fe respiration. The reducibility of U(VI) could impact the fate of U(IV) by controlling mineral precipitation reactions, which has implications for the long-term immobilization of U in subsurface environments. Here, we studied anoxic cultures of Shewanella putrefaciens CN32 incubated with natural carnotite-group minerals by X-ray diffraction, electron microscopy, scanning transmission X-ray microscopy (STXM). Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy measurements at U-N 4,5 , V-L 2,3 , and O-K edges on cultures incubated up to 10 months show that V(V) was reduced to V(IV), whereas U was not reduced. In contrast, V(V) and U(VI) in solution were both completely reduced to lower oxidation states by CN32, as precipitates within the exopolymer surrounding the bacteria. Assays for the toxicity of U and V to CN32 showed that biofilm formation was stimulated at 0.001 M U(VI), and growth was inhibited at concentrations of U(VI) greater than 0.001 M. Vanadium did not inhibit growth or stimulate biofilm formation at any concentration tested. Investigations of the bacteria-mineral and bacteria-metal interface at the nanometer and molecular scales provide new insights into the co-respiration of V and U that help explain their biogeochemical cycling and have implications for subsurface bioremediation of these elements.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Geologic hydrogen: From natural occurrences to anthropogenic generation – A review of fundamentals, potential, challenges and prospects

Growing demand for hydrogen is exposing the environmental and economic limits of reforming-based and carbon-managed supply chains, while the scale-up of electrolytic capacity remains capital-constrained. Geologic hydrogen, defined as molecular H₂ generated and stored within the Earth's crust offers a complementary, potentially lower-cost resource, yet exploration is still ad hoc. This review (1) revisits a global inventory of confirmed hydrogen seeps and subsurface occurrences; (2) analyzes the controlling reactions, migration pathways, and trapping conditions governing these occurrences; (3) proposes a process-based geologic hydrogen system concept analogous to, yet distinct from, the petroleum system; and (4) evaluates potential geologic hydrogen systems within the United States as a representative case study. Here, we contrast natural systems powered by serpentinization, mantle degassing or radiolysis with anthropogenic systems that stimulate the same reactions or convert in-situ hydrocarbons. Stable hydrogen accumulations require generation rates that outpace combined physical, chemical and microbial losses; the Bourakébougou field (Mali) exemplifies a self-recharging, free-gas reservoir sustained by meteoric-water serpentinization beneath an efficient caprock. Prospective geologic hydrogen resources are likely to occur in regions where iron-rich lithologies, deep-seated faults, and low-permeability sealing formations coexist. Applying this principle, we highlight three promising hydrogen play types in U.S. geological terrains: ophiolite belts (Appalachian and Californian regions), the Midcontinent Rift and the Lake Superior banded‑iron formations. Multiphysics numerical models and positive-unlabeled machine-learning workflows help to accelerate play screening and de-risk future production; yet, reaction kinetics, stimulation strategies, and full techno-economic and life-cycle assessments remain pivotal knowledge gaps.

Anthropogenic hydrogen generation↗
DOE OSTI2022

Effect of bacterial cell addition on Fe(III) reduction and soil organic matter transformation in a farmland soil

The coupled biogeochemical processes of Fe(III) reduction and organic matter transformation profoundly impact terrestrial carbon cycling. However, little is known about the microbial role in soil organic matter (SOM) transformation during Fe(III) bio-reduction. Here we investigated the bio-reduction behavior of a black farmland soil and corresponding SOM transformation under circumneutral and anoxic conditions. A model dissimilatory Fe reducing bacterium, Geobacter sulfurreducens, was added in either live or dead form in order to enhance Fe(III) reduction in soil and to evaluate the accompanying transformation of SOM. The progress of Fe reduction was monitored and SOM transformation was characterized by various spectroscopy methods. Results showed that addition of either dead or live G. sulfurreducens cells increased the Fe(III) reduction rate and extent. Without cell addition, SOM transformation was insignificant within 13 days of incubation, only with some consumption of aliphatic/protein compounds, apparently due to their higher bio-degradability. Addition of dead or live cells resulted in more drastic SOM transformation, but through different mechanisms. With dead cell amendment, cell necromass and debris stimulated the activity of indigenous soil microbes by serving as extra carbon/energy sources. During Fe(III) reduction, the aliphatic/protein compounds were preferentially consumed by indigenous microbial communities, similar to the treatment without cell addition but with a greater extent of consumption. In comparison, addition of live G. sulfurreducens cells stimulated degradation of less bioavailable compounds, including more saturated and higher molecular weight SOM. It is possible that fast depletion of labile SOM by live G. sulfurreducens cells favored utilization of less bioavailable molecules (such as those with more aromatic structures) by the originally dormant species in native microbial community, suggesting an active role of live Fe(III)-reducing bacteria in affecting SOM transformation. In addition, fast assimilation of microbial related carbon, such as aromatic proteins and microbial byproducts, into SOM pools was also observed. Overall, our results suggest that addition of Fe(III)-reducing bacteria to a native soil can enhance Fe(III) reduction and accelerate the turnover of SOM through various mechanisms. The study provides new insights into coupled Fe(III) reduction and SOM transformation, as well as the “priming effect” of SOM using microbial cells as substrate.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

3D seismic imaging of a fracture damage zone controlling reservoir compartmentalization at the Raft River EGS using multi-azimuth walkaway VSP

Accurate imaging of steeply dipping fracture zones in crystalline enhanced geothermal systems (EGS) is critical for constraining permeability architecture and guiding stimulation design. However, such structures remain poorly resolved by conventional surface seismic methods. We present a fully three-dimensional (3D) elastic-waveform inversion-migration workflow applied to multi-azimuth walkaway vertical seismic profiling (VSP) data acquired in a deviated borehole at the Raft River EGS. The workflow integrates first-arrival traveltime tomography, multi-scale elastic waveform inversion (EWI), and elastic least-squares reverse-time migration (ELSRTM) to recover high-resolution compressional-and shear-wave velocity models and to image structural discontinuities in the crystalline basement. The results reveal a laterally continuous low-velocity anomaly, with shear-wave velocity reductions of 25-30%, consistent with fractureinduced mechanical weakening. Two steeply dipping discontinuities bound a 50-80 m wide fracture damage zone. Independent constraints from microseismic clustering and geochemical compartmentalization corroborate the geometry and structural significance of this feature. Synthetic modeling further confirms that structures of this scale are resolvable (~30 m). These findings indicate that the Narrows structure is a distributed fracture damage zone rather than a discrete fault plane. By resolving fracture-zone geometry at the tens-of-meters scale using a single borehole, this workflow provides a practical and transferable approach for improving structural characterization, reducing uncertainty in permeability architecture, and supporting reservoir modeling and stimulation design in fractured crystalline EGS reservoirs.

58 GEOSCIENCES↗
DOE OSTI2022

Experimental study of fracture slip due to stress perturbation in fractured geo-resources

Anthropogenic activities such as underground fluid injection/extraction, well stimulation, and dam impoundment will perturb the state-of-stress in the subsurface, which could activate critically stressed pre-existing fractures and faults. Fault and fracture activation can induce seismicity, change flow behavior, and damage asperities on the fracture surface to alter reservoir permeability. Here, in this study, triaxial shear tests were conducted on saw cut and rough fracture Barre granite specimens to better characterize how a decrease in normal stress and increase in shear stress will influence crystalline rock fracture hydromechanical properties. In a triaxial set up, confining pressure (CP) and differential stress (DS) were used to induce normal and shear stress on a 45° oriented fracture. Fracture slip and the corresponding stress relaxation was observed when the confining stress decreased. Fracture permeability increased when the fracture slipped. Moreover, new micro-cracks observed by x-ray images indicated the creation of new flow paths for fluid movement. The experimental outcomes of this study indicate that decrease in normal stress due to stress perturbations along the faults/fractures in the extensional stress regime can induce the slip along the fracture. This could have a significant influence on slope stability in quarries, stimulation and injection strategy in deep geo-resources, and potentially minimize the risk of induced seismicity. The observed stress dependency of hydraulic aperture in rough fracture during pre- and post-slip stages could provide key inputs for field-scale simulation of geo-resources.

58 GEOSCIENCES↗
DOE OSTI2021

Structural delineation and phase-dependent activation of the costimulatory CD27:CD70 complex

CD27 is a tumor necrosis factor (TNF) receptor, which stimulates lymphocytes and promotes their differentiation upon activation by TNF ligand CD70. Activation of the CD27 receptor provides a costimulatory signal to promote T cell, B cell, and NK cell activity to facilitate antitumor and anti-infection immunity. Aberrant increased and focused expression of CD70 on many tumor cells renders CD70 an attractive therapeutic target for direct tumor killing. However, despite their use as drug targets to treat cancers, the molecular basis and atomic details of CD27 and CD70 interaction remain elusive. Here we report the crystal structure of human CD27 in complex with human CD70. Analysis of our structure shows that CD70 adopts a classical TNF ligand homotrimeric assembly to engage CD27 receptors in a 3:3 stoichiometry. By combining structural and rational mutagenesis data with reported disease-correlated mutations, we identified the key amino acid residues of CD27 and CD70 that control this interaction. We also report increased potency for plate-bound CD70 constructs compared with solution-phase ligand in a functional activity to stimulate T-cells in vitro. These findings offer new mechanistic insight into this critical costimulatory interaction.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Transcriptional networks underlying a primary ovarian insufficiency disorder in alligators naturally exposed to EDCs

Interactions between the endocrine system and environmental contaminants are responsible for impairing reproductive development and function. Despite the taxonomic diversity of affected species and attendant complexity inherent to natural systems, the underlying signaling pathways and cellular consequences are mostly studied in lab models. To resolve the genetic and endocrine pathways that mediate affected ovarian function in organisms exposed to endocrine disrupting contaminants in their natural environments, we assessed broad-scale transcriptional and steroidogenic responses to exogenous gonadotropin stimulation in juvenile alligators (Alligator missippiensis) originating from a lake with well-documented pollution (Lake Apopka, FL) and a nearby reference site (Lake Woodruff, FL). Here, we found that individuals from Lake Apopka are characterized by hyperandrogenism and display hyper-sensitive transcriptional responses to gonadotropin stimulation when compared to individuals from Lake Woodruff. Site-specific transcriptomic divergence appears to be driven by wholly distinct subsets of transcriptional regulators, indicating alterations to fundamental genetic pathways governing ovarian function. Consistent with broad-scale transcriptional differences, ovaries of Lake Apopka alligators displayed impediments to folliculogenesis, with larger germinal beds and decreased numbers of late-stage follicles. After resolving the ovarian transcriptome into clusters of co-expressed genes, most site-associated modules were correlated to ovarian follicule phenotypes across individuals. However, expression of two site-specific clusters were independent of ovarian cellular architecture and are hypothesized to represent alterations to cell-autonomous transcriptional programs. Collectively, our findings provide high resolution mapping of transcriptional patterns to specific reproductive function and advance our mechanistic understanding regarding impaired reproductive health in an established model of environmental endocrine disruption.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Environmental impact of solution pH on the formation and migration of iron colloids in deep subsurface energy systems

Deep subsurface stimulation processes often promote fluid-rock interactions that can lead to the formation of small colloidal particles that are suspected to migrate through the rock matrix, partially or fully clog pores and microfractures, and promote the mobilization of contaminants. Thus, the goal of this work is to understand the geochemical changes of the host rock in response to reservoir stimulation that promote the formation and migration of colloids. Two different carbonate-rich shales were exposed to different solution pHs (pH = 2 and 7). In this study, iron and other mineral transformations at the shale-fluid interface were first characterized by synchrotron-based XRF mapping. Then, colloids that were able to migrate from the shale into the bulk fluid were characterized by synchrotron-based extended X-ray absorption structure (EXAFS), scanning electron microscopy (SEM), and single-particle inductively coupled plasma time-of-flight mass spectrometry (sp-icpTOF-MS). When exposed to the pH = 2 solution, extensive mineral dissolution and secondary precipitation was observed; iron-(oxyhydr)oxide colloids colocated with silicates were observed by SEM at the fluid-shale interfaces, and the mobilization of chromium and nickel with these iron colloids into the bulk fluid was detected by sp-icpTOF-MS. Iron EXAFS spectra of the solution at the shale-fluid interface suggests the rapid (within minutes) formation of ferrihydrite-like nanoparticles. Thus, we demonstrate that the pH neutralization promotes the mobilization of existing silicate minerals and the rapid formation of new iron colloids. These Fe colloids have the potential to migrate through the shale matrix and mobilize other heavy metals (such as Cr and Ni, in this study) and impacting groundwater quality, as well produced waters from these hydraulic fracturing operations.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Priming mechanisms providing plants and microbes access to mineral-associated organic matter

Mineral-associated organic matter (MAOM) is considered a stable reservoir for soil nutrients that influences long-term soil carbon (C) and nitrogen (N) dynamics. However, recent experimental and theoretical evidence shows that root exudates may mobilize MAOM, thereby providing plants and microbes access to a large and N-rich pool. Given the mechanisms underlying MAOM C and N mobilization remain largely untested, we examined direct and indirect pathways by which root exudates destabilize this nutrient pool in laboratory mesocosms. We simulated root exudation with 13 C-labeled oxalic acid to test whether root exudates are directly capable of mobilizing MAOM from mineral surfaces; and with 13 C-labeled glucose to test whether indirect stimulation of microbial and extracellular enzyme activity leads to MAOM decomposition. We also tested the potential for oxalic acid and glucose to mobilize MAOM in an additional subset of sterilized soils to clarify the potential for non-microbial pathways of MAOM destabilization. Over the course of the 12-day MAOM incubation with and without simulated exudates, we measured C cycling (CO 2 respiration rates, 13 C–CO 2 efflux), N cycling (inorganic N pools, gross N mineralization) and related microbial processes (enzyme activities and microbial community composition via phospholipid fatty acid analysis). Both of the simulated root exudates enhanced MAOM-C mineralization, with cumulative respiration increasing 35–89% relative to the water-only control. Likewise, glucose additions enhanced the production of an exo-cellulase and a chitinase by up to 130% and 39%, respectively, while oxalic acid enhanced oxidative enzyme activities up to 91% greater than control rates. We observed a positive association between glucose-induced shifts in enzyme activities, MAOM-C mineralization, and gross ammonification. Oxalic acid additions were associated with initial increases in fungal relative abundance and in sterile soils appeared to stimulate the release of metals and dissolved organic nitrogen into exchangeable pools. Our results indicate that common root exudates, like glucose and oxalic acid, can significantly increase the turnover and potential release of C and N from MAOM through indirect (e.g., enzyme induction) and direct (e.g., mobilization of metal oxides) mechanisms.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Getting to the root of the problem: Soil carbon and microbial responses to root inputs within a buried paleosol along an eroding hillslope in southwestern Nebraska, USA

Large quantities of soil carbon (C) can persist within paleosols for millennia due to burial and subsequent isolation from plant-derived inputs, atmospheric conditions, and microbial activity at the modern surface. Erosion exposes buried soils to modern root-derived C influx via root exudation and root turnover, thus stimulating microbial activity leading to SOC decomposition and accumulation through organo-mineral stabilization of modern C. With this study we aim to quantify how modern root-derived C inputs impact paleosol C decomposition and stabilization across varying degrees of isolation from modern surface conditions in southwestern Nebraska, USA, where hillslope erosion is bringing a buried Late-Pleistocene-early Holocene paleosol (the “Brady Soil”) closer to the modern surface. We collected Brady Soil samples from 0.2m, 0.4m, and 1.2m below the modern surface and conducted two lab-based incubations. Soils were amended with either (1) a lab-synthesized mixture of low molecular weight compounds (12 atom% 13 C), or (2) 13 C enriched root residues (92 atom% 13 C), in 30-day and 240-day incubation experiments, respectively. Here we determined microbial responses to synthetic root exudates and residues by partitioning the 13 C label from Brady Soil C, including measurements of total, root, and primed C respiration, microbial biomass C (MBC), microbial C use efficiency (CUE). To assess the capacity of isolated paleosols to accrue modern plant C, we used Nano-scale Secondary Ion Mass Spectrometry imaging. We found that: (1) adding root-derived C inputs primed Brady Soil C across all depths, and was mediated by depth and composition of root additions; (2) root-derived C inputs stimulated microbial biomass C (MBC) growth similarly across depths, but the magnitude of CUE and MBC varied by chemistry of root-derived additions; (3) new particulate organic matter was incorporated into mineral-associated pools over time; (4) material from the added root residues was found in association with bacterial cells and fungal hyphae as well as with soil aggregate and mineral surfaces. Our study shows that paleosols defy expectations of C content and reactivity with depth, and changes in land cover and climate will expose buried paleosols to modern surface conditions, increasing respired C. This work highlights the importance of evaluating the role resurfacing buried soils through landscape change plays in C cycle feedbacks to the climate system.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

The contribution of the neuroendocrine system to adaption after repeated daily ozone exposure in rats

Ozone-induced lung injury/inflammation dissipates despite continued exposure for 3 or more days; however, the mechanisms of adaptation/habituation remain unclear. Since ozone effects are mediated through adrenal-derived stress hormones, which also regulate longevity of centrally-mediated stress response, we hypothesized that ozone-adaptation is linked to diminution of neuroendocrine stress-axes activation and glucocorticoid levels. Male Wistar-Kyoto-rats (12-week-old) were injected with vehicle or a therapeutically-relevant dexamethasone dose (0.01-mg/kg/day; intraperitoneal) for 1-month to determine if suppression of glucocorticoid signaling was linked to adaptation. Vehicle- and dexamethasone-treated rats were exposed to air or 0.8-ppm ozone, 4 h/day × 2 or 4 days to assess the impacts of acute exposure and adaptation, respectively. Dexamethasone reduced thymus and spleen weights, circulating lymphocytes, corticosterone and increased insulin. Ozone increased lavage-fluid protein and neutrophils and decreased circulating lymphocytes at day-2 but not day-4. Ozone-induced hyperglycemia, glucose intolerance and inhibition of beta-cell insulin release occurred at day-1 but not day-3. Ozone depleted circulating prolactin, thyroid-stimulating hormone, and luteinizing-hormone at day-2 but not day-4, suggesting central mediation of adaptation. Adrenal epinephrine biosynthesis gene, Pnmt, was up-regulated after ozone exposure at both timepoints. However, genes involved in glucocorticoid biosynthesis were up-regulated after day-2 but not day-4, suggesting that acute 1- or 2-day ozone-mediated glucocorticoid increase elicits feedback inhibition to dampen hypothalamic stimulation of ACTH release in response to repeated subsequent ozone exposures. Although dexamethasone pretreatment affected circulating insulin, lymphocytes and adrenal genes, it had modest effect on ozone adaptation. In conclusion, ozone adaptation likely involves lack of hypothalamic response due to reduced availability of circulating glucocorticoids.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Novel method for effectively amplifying human peripheral blood T cells in vitro

The use of chimeric antigen receptor-modified T cells (CAR T cells) is an effective therapy for advanced cancer, especially hematological malignancies, and this method has attracted widespread attention in the last several years. The type, number and vitality of the effector cells clearly play important roles in this approach. In this study, to expand the possibility of curing cancer through adoptive cell therapy (ACT), we developed a novel method for effectively obtaining abundant T cells in vitro. The fusion proteins of three cytokines, SA-hIL-2, SA-hIL-7 and SA-hIL-21, were anchored onto biotin magnetic beads to increase the number of cytokines on the surface of the magnetic beads, which increased the local concentration of cytokines and thus promoted the binding of cytokines to T cells. Next, we examined the effects of these modified magnetic beads on the proliferation rate of T cells and CD19 CAR T cells. In this study, we report the expression and purification of the active bifunctional fusion proteins SA-hIL-2, SA-hIL-7 and SA-hIL-21, which were bound to biotin magnetic beads to develop a platform that was employed to increase the local concentration of cytokines. When the cells had been cultured for 14 days, the proliferation rate of the CD3{sup +} T cells in the group that received cytokine-coupled biotin magnetic beads (Beads-SA-CK) was higher than that of the cells in the groups that received soluble cytokines (Soluble-SA-CK) and that of the cells in the standard group (Standard-CK). We speculate that this difference may be the result of the increased expression of Bcl-2 and the increased phosphorylation of Stat5. Moreover, our results preliminarily indicate that compared with the other two treatments, Soluble-SA-CK and Standard-CK, adding cytokine-coupled biotin magnetic beads more effectively increases the proliferation rate of CD19 CAR-T cells. As expected, the CD19 CAR-T cells stimulated by Beads-SA-CK had a stronger anticancer effect than the cells stimulated by the other two treatments. An effective method of preparing abundant T cells in vitro was developed, and it may provide a novel strategy for ACT.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Down-regulation of A3AR signaling by IL-6-induced GRK2 activation contributes to Th17 cell differentiation

Highlights: • Cyclic AMP-PKA signaling is involved in Th17 cell differentiation. • IL-6 stimulation triggers the internalization of A{sub 3}AR and promotes cAMP production in T cells. • IL-6 induces A{sub 3}AR internalization in a GRK2 dependent manner. • GRK2 is a potential therapeutic target for treating Th17 driving immune diseases. IL-6-triggered Th17 cell expansion is responsible for the pathogenesis of many immune diseases including rheumatoid arthritis (RA). Traditionally, IL-6 induces Th17 cell differentiation through JAK-STAT3 signaling. In the present work, PKA inhibition reduces in vitro induction of Th17 cells, while IL-6 stimulation of T cells facilitates the internalization of A{sub 3}AR and increased cAMP production in a GRK2 dependent manner. Inhibition of GRK2 by paroxetine (PAR) or genetic depletion of GRK2 restored A{sub 3}AR distribution and prevented Th17 cell differentiation. Furthermore, in vivo PAR treatment effectively reduced the splenic Th17 cell proportion in a rat model of collagen-induced arthritis (CIA) which was accompanied by a significant improvement in clinical manifestations. These results indicate that IL-6-induced Th17 cell differentiation not only occurs through JAK-STAT3-RORγt but is also mediated through GRK2-A{sub 3}AR-cAMP-PKA-CREB/ICER-RORγt. This elucidates the significance of GRK2-controlled cAMP signaling in the differentiation of Th17 cells and its potential application in treating Th17-driven immune diseases such as RA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Protective effect of SIRT6 on cholesterol crystal-induced endothelial dysfunction via regulating ACE2 expression

Highlights: • ACE2 was involved in CC-induced endothelial dysfunction. • SIRT1 and SIRT6 contributed to regulating the protein expression of ACE2 in CC-stimulated endothelial cells. • SIRT6 regulated ACE2 with intranuclear p-ATF2, but not affecting p-ATF2 expression in the cytoplasm. Sirtuins are a family of highly conserved nicotinamide adenine dinucleotide (NAD{sup +})-dependent enzymes. Among the sirtuins, SIRT1 and SIRT6 participate in the regulation of endothelial functions and play significant roles in the physiological and pathological processes of cardiovascular diseases (CVD). Recently, our study found that minute cholesterol crystals (CC) can be endocytosed by endothelial cells and further impair endothelial functions. Since previous studies have reported that angiotensin-converting enzyme (ACE2) involves Angiotensin (Ang) II-induced inflammation in endothelial cells, this study was designed to investigate the role of SIRT1 and SIRT6 in CC-induced variation of ACE2 expression and the related mechanism between SIRT6 and ACE2. We found that ACE2 is involved in CC-induced endothelial dysfunction, which inhibits decreases in nitric oxide (NO) level and endothelial nitric oxide synthase (eNOS) activity and increases in inflammatory factors and adhesion molecules. Besides, SIRT1 and SIRT6 regulated the protein expression of ACE2 in CC-stimulated human umbilical vein endothelial cells (HUVECs). Moreover, bioinformatics analysis from the Enrichr database indicated that activating transcription factor 2 (ATF2), is highly correlated with genes that significantly upregulated after infection with the SIRT6 adenovirus vector. In CC-induced HUVECs, ACE2 expression was up-regulated in cells transfected with ATF2 siRNA. However, further mechanism studies revealed that overexpression of SIRT6 decreases the accumulation of p-ATF2 in the nucleus, but did not affect p-ATF2 expression in the cytoplasm. Taken together, these data indicated that SIRT6 regulates ACE2 might via inhibiting the accumulation of nucleus p-ATF2 in CC-induced endothelial dysfunction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Glucocorticoids suppressed osteoblast differentiation by decreasing Sema3A expression via the PIK3/Akt pathway

Highlights: • Dex decreased Sema3A expression by suppressing the PI3K/Akt pathway. • Sema3A reversed Dex-induced suppression of osteoblast differentiation. • Sema3A reversed the Dex-mediated reduced transcriptional activity of β-catenin. Glucocorticoids(GCs) are extensively used to treat inflammatory and autoimmune diseases. Excessive prolonged exposure to glucocorticoids is associated with an increased risk of osteoporosis. The inhibition of osteoblast differentiation by GCs is suggested as a major cause for GCs-induced osteoporosis (GIO). However, the precise mechanism underlying the role of GCs in osteoblasts differentiation is not fully elucidated. Semaphorin 3A (Sema3A), a secreted member of the Semaphorin family, enhances bone formation and promotes fracture healing, which is known to increase osteoblastic differentiation and stimulate osteogenesis in bone metabolism. Here, the present study explored the effect of Sema3A in osteoblast differentiation using dexamethasone (Dex) treatment of bone marrow stromal cells (BMSCs). Dex treatment decreased Sema3A expression in BMSCs in a dose-dependent manner. Moreover, Dex stimulation suppressed the differentiation of osteoblasts by reducing alkaline phosphatase (ALP) activity, osteoblastic marker genes expression and mineralization, but all of these effects were ameliorated by exogenous recombinant Sema3A administration. Furthermore, exogenous Sema3A administration reversed the Dex-mediated decrease in nuclear accumulation of β-catenin and β-catenin activity in BMSCs. Meanwhile, Dex was capable of simultaneously suppressing the phosphorylation of protein kinase B(Akt) and the expression level of Sema3A in BMSCs. These changes were significantly abolished by the PI3K/Akt agonist. These results suggest that Dex inhibits osteoblast differentiation by suppressing Sema3A expression via the PI3K/Akt pathway. These data provide new insights into the molecular mechanisms of Dex-induced osteoblast differentiation inhibition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

NF-κB and neutrophil extracellular traps cooperate to promote breast cancer progression and metastasis

Highlights: • Cancer cells–derived factors, such as IL-8 and G-CSF, induce NETs formation via PAD4 and NF-κB. • NETs increase the interaction of NEMO with IKKα/β and enhance NF-κB activation. • Blockade of NETs using PAD4 inhibitor decreases NF-κB and tumor metastasis. • Selective inhibition of NF-κB reduces NETs formation and tumor growth and metastasis. Aberrant NF-κB activation and neutrophil extracellular traps (NETs) are associated with breast cancer progression. How NF-κB and NETs modulate each other in breast cancer development remains unclear. Here, we found that NETs induced by phorbol 12-myristate 13-acetate promote breast cancer cell progression. In turn, cancer cells–derived factors, such as IL-8 and granulocyte colony-stimulating factor, stimulate neutrophils to form NETs. Mechanistically, NETs increased the interaction of NF-κB essential modifier (NEMO) with IκB kinase (IKK)α/β and enhanced NF-κB activation. We then employed a cell-permeable peptide corresponding to the NEMO-binding domain (NBD) of IKKα/β, termed NBD peptide, which disrupts NETs-mediated NEMO interaction with IKKα/β and abolished NF-κB activation in vitro. NBD peptide also reduced IL-8 level and NETs formation, and suppressed primary tumor growth and/or lung metastasis in human breast cancer mouse xenograft models and mouse spontaneous breast cancer model. Blockade of NET formation using a peptidylarginine deiminase 4 (PAD4) pharmacologic inhibitor decreased NF-κB activation and tumor metastasis. Collectively, these data suggest that NF-κB associates with NETs to form a positive loop facilitating breast tumor progression and metastasis, and that selective inhibition of NF-κB and PAD4-dependent NETs provides an effective therapeutic approach for treating breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A Critical Review of the Physicochemical Impacts of Water Chemistry on Shale in Hydraulic Fracturing Systems

Hydraulic fracturing of unconventional hydrocarbon resources involves the sequential injection of a high-pressure, particle-laden fluid with varying pH’s to make commercial production viable in low permeability rocks. This process both requires and produces extraordinary volumes of water. The water used for hydraulic fracturing is typically fresh, whereas “flowback” water is typically saline with a variety of additives which complicate safe disposal. As production operations continue to expand, there is an increasing interest in treating and reusing this high-salinity produced water for further fracturing. Here in this paper we review the relevant transport and geochemical properties of shales, and critically analyze the impact of water chemistry (including produced water) on these properties. We discuss five major geochemical mechanisms that are prominently involved in the temporal and spatial evolution of fractures during the stimulation and production phase: shale softening, mineral dissolution, mineral precipitation, fines migration, and wettability alteration. A higher salinity fluid creates both benefits and complications in controlling these mechanisms. For example, higher salinity fluid inhibits clay dispersion, but simultaneously requires more additives to achieve appropriate viscosity for proppant emplacement. In total this review highlights the nuances of enhanced hydrogeochemical shale stimulation in relation to the choice of fracturing fluid chemistry.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Binding of Formic Acid on Anatase TiO2(101)

The adsorption of formic acid (FA) and the formation of formate species on metal oxide surfaces are of great interest in catalysis. Formic acid is used to probe the adsorption properties of surface sites and formates are common intermediates in many catalytic reactions. Here we focus on the interaction of FA with a prototypical anatase TiO2(101) surface by using a combination of scanning tunneling microscopy (STM), infrared reflection absorption spectroscopy (IRAS), electron stimulated desorption (ESD), and density functional theory (DFT) to assess the coverage dependent evolution of different FA-derived surface species at low temperatures (80–240 K). We find that isolated FA adsorbs at 80 K in both monodentate (MD) and bidentate (BD) configurations on top of undercoordinated Ti sites (Ti5c). The MD form is likely deprotonated and readily converts upon annealing to bridging BD on two neighboring Ti5c sites. DFT calculations show that molecularly-bound MD FA is metastable and readily converts into a deprotonated state in the proximity of subsurface oxygen vacancy. The stability of the MD species increases as the availability of the paired Ti5c sites for BD formation diminishes at high coverages. Upon surface saturation, a mixed configuration of alternating bidentate and monodentate species with coverage of 2/3 FA/Ti5c represents the most favorable configuration. This is in contrast with the adsorption of FA on rutile TiO2(110) and many other oxides, where bidentate formate species dominate. Y.W., A.D., G.A.K., R.R., N.G.P., and Z.D. were supported by the U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences (BES), Division of Chemical Sciences, Geosciences and Biosciences (CSGB) under FWP 47319. B.W. and A.S. acknowledge the support of DOE BES, CSGB Division under Award DESC0007347. The experimental studies were performed in EMSL, a national scientific user facility sponsored by the Department of Energy’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is a multiprogram national laboratory operated for DOE by Battelle. The authors also acknowledge computational resources from the TIGRESS high-performance computer center at Princeton University.

Wang, Yang↗