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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 559 records · Page 31
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Precipitation and nitrogen application stimulate soil nitrous oxide emission

Precipitation and nitrogen (N) fertilization are the two most important drivers for soil nitrous oxide (N 2 O) emission. However, the effects of changes in N fertilization and precipitation patterns (i.e., precipitation intensity and frequency) on N 2 O emissions in agricultural fields are still unclear. In this study, we simulated soil N 2 O emission under different precipitation patterns (6 precipitation intensities, and 12 precipitation frequencies by either merging or splitting precipitation events) and N fertilization rates (low, typical, and high N fertilization) in a cornfield using the DeNitrification-DeComposition model. The model was parameterized and validated using meteorological data and N experimental measurements in Nashville, Tennessee, USA. Results showed that soil water filled pore space (WFPS) and simulated soil N 2 O emission increased as precipitation intensity increased. Less frequent but high intensity precipitation treatments reduced the soil WFPS by 25.2% and stimulated soil N 2 O emission by 45.3%, while more frequent but low intensity precipitation treatments increased soil WFPS by 9.0% and reduced soil N 2 O emission by 23.9%. Compared to typical N fertilization, the sensitivity of soil N 2 O emission to precipitation was higher under high N than low N fertilization treatments, and the response ratios were 50.0% and 40.1%, respectively. There was significant interactive effect of precipitation intensity and N fertilization on soil N 2 O emission. Furthermore, these findings improved our understanding of precipitation and N impacts on soil N 2 O emissions and provided useful knowledge for irrigation and N fertilizer management in agriculture to mitigate greenhouse gas emissions.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Photonic generation of millimeter-wave ultra-wideband monocycle signal using up-conversion based on stimulated Brillouin scattering effect

We propose a novel scheme for photonic generation of millimeter-wave (MMW) ultra-wideband monocycle signal free of strong local oscillation (LO) and low-frequency component. A theory and a mathematical model are built to investigate the proposed scheme. Firstly, a differentiator is implemented using a dual-drive Mach–Zehnder modulator to attain monocycle pulses by differentiating a series of Gauss pulses. Subsequently, a dual-parallel Mach–Zehnder modulator and stimulated Brillouin scattering effect are employed to realize single-sideband modulation for up-converting the monocycle pulses to the MMW band. In the calculation, the generated signal is centered at 26 GHz with 10-dB bandwidth of 7 GHz and its power efficiency is about 50.08%. In addition, on–off keying modulation, amplitude modulation (PAM) and pulse position modulation monocycle pulses are generated. The spectrum of the generated signal meets with the FCC mask efficiently, so this technique has a potential application in MMW radar communication systems.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2019

Wideband tunable up-converting optoelectronic oscillator based on gain–loss compensation technology and stimulated Brillouin scattering

An optically wideband tunable up-converting optoelectronic oscillator (OEO) based on stimulated Brillouin scattering and gain–loss compensation is demonstrated and theoretically analyzed. In the proposed structure, Brillouin narrowband filter technique is implemented by introducing two pump lights with the frequency interval twice the Brillouin frequency shift (v{sub b}). The overlapping of the gain and the loss spectrum is used to realize a wideband tunable OEO. As a consequence, the tunability of the wideband of the output microwave signal at f{sub m}+2v{sub b} from 22.4 to 61.4 GHz can be realized by changing the signal under testing from 1 to 40 GHz. In addition, the transfer function of the system is given and the single sideband (SSB) phase noise is also evaluated theoretically. And the theoretical simulated the SSB phase noise is − 116.1 dBc/Hz at the 10 kHz offset when the f{sub m} = 25 GHz. Not only the OEO can convert a low-frequency IF signal to a high-frequency signal without introducing any high-Q electrical filter, but the frequency of the output signal is high enough and widely tunable. Because of the high frequency tunable capacity, the up-converting OEO might have a potential application in radar communication and millimeter wave generation systems.

42 ENGINEERING↗
DOE OSTI2017

Tris(2-hydroxyethyl)ammonium arylchalcogenylacetates, growth stimulants of alcohol yeast Saccharomyces cerevisiae

A number of tris(2-hydroxyethyl)ammonium arylchalcogenylacetates ArYCH{sub 2}CO{sub 2}{sup –}• •HN{sup +}(CH{sub 2}CH{sub 2}OH){sub 3} (1—4) (Ar = aryl; Y = O, S, SO{sub 2}) were synthesized. Their structure was established by IR and {sup 1}H, {sup 13}C, {sup 15}N NMR spectroscopy. The influence of compounds 1—4 on the growth and development of yeast fungi Saccharomyces cerevisiae was studied. Compounds 1—4 were found to be efficient, safe, and available synthetic stimulants of these processes. The use of compounds 1—4 in low concentrations (from 10{sup –8} to 10{sup –4} wt.%, depending on the time of cultivation, concentration, and the anion type) reduced the lag-phases of development and increased the generation rate of yeast cells by 2—5 times. The amount of yeast cells increased by 2—3 times, while the content of protein in the biomass increased by 13—15%. The fermentation of sugar- and starch-containing raw material with yeast Saccharomyces cerevisiae increased the yield of ethyl alcohol (biofuel) by 5—9%.

09 BIOMASS FUELS↗
DOE OSTI2019

Ultra-Shallow Doping B, Mg, Ni, Cu, Mn, Cr and Fe into SiC with Very High Surface Concentrations Based on Plasma Stimulated Room-Temperature Diffusion

Very recently, we reported a novel doping method called plasma doping without any external bias (PDWOEB) for the introduction of some impurities into Si and GaN at room temperature (RT). In this work, the RT doping of some impurities, including B, Mg, Ni, Cu, Mn, Cr and Fe, into SiC with ultra-shallow depths of tens of nanometer and very high surface concentrations, approaching or exceeding 1E20/cm{sup 3}, by using PDWOEB is reported. It has been found for the first time that the doping depths and surface concentrations of these impurities doped into SiC by the PDWOEB increase drastically with increasing doping time and the ferromagnetism of SiC due to Ni doping is demonstrated. Moreover, the approximate diffusivities of B, Mg, Ni, Cu, Mn, Cr and Fe in SiC at RT under plasma stimulation are obtained. The physical mechanism of PDWOEB is further discussed, and some unclear viewpoints are clarified.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia

Microglia, resident macrophages of the central nervous system (CNS), is responsible for immune responses and homeostasis of the CNS. Microglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Therefore, therapeutic agents that suppress the microglia-mediated inflammatory response could potentially be used in the prevention or treatment of neurodegenerative diseases. Vanillin, a primary component of vanilla bean extract, has anti-inflammatory, anticancer, and antitumor properties. However, the effects of vanillin on the anti-neuroinflammatory responses of microglial cells are still poorly understood. In this study, we investigated the mechanism by which vanillin induces anti-neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that vanillin significantly decreased the production of nitric oxide and pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Vanillin also reduced the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the mRNA expression levels of IL-1β, TNF-α, and IL-6. Moreover, vanillin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. Collectively, these results suggest that vanillin has anti-neuroinflammatory properties and may act as a natural therapeutic agent for neuroinflammatory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Stimulated Motion Suppression (STMS): a New Approach to Break the Resolution Barrier for Ion Trap Mass Spectrometry

Ion trap is an excellent platform to perform tandem mass spectrometry (MS/MS), but has an intrinsic drawback in resolving power. Using ion resonant ejection as an example, the resolution degradation can be largely attributed to the broadening of the resonant frequency band (RFB) between ion motion and driving alternative-current (AC). To solve this problem, stimulated motion suppression (STMS) was developed. The key idea of STMS is the use of two suppression alternative-current (SAC) signals, which both have reversed initial phases to the main AC. The SACs can block the unexpected sideband ion resonances (or ejections), therefore playing a key role in sharpening the RFB. The proof-of-concept has been demonstrated through ion trajectory simulations and validated experimentally. STMS provides a new and versatile means for the improvement of the ion trap resolution, which for a long time has reached the bottleneck through conventional methods, e.g., increasing the radio-frequency (RF) voltage and decreasing the mass scan rate. At the end, it is worth noting that the idea of STMS is very general and principally can be applied in any RF device for the purposes of high-resolution mass analysis and ion isolation. .

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2013

Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs/NF-κB signaling pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes

Highlights: •Nebivolol may act as a partial agonist of β3-adrenergic receptor (AR). •Nebivolol stimulates mitochondrial DNA replication and protein expression. •Nebivolol promotes mitochondrial synthesis via activation of eNOS by β3-AR. -- Abstract: Nebivolol is a third-generation β-adrenergic receptor (β-AR) blocker with additional beneficial effects, including the improvement of lipid and glucose metabolism in obese individuals. However, the underlying mechanism of nebivolol’s role in regulating the lipid profile remains largely unknown. In this study, we investigated the role of nebivolol in mitochondrial biogenesis in 3T3-L1 adipocytes. Exposure of 3T3-L1 cells to nebivolol for 24 h increased mitochondrial DNA copy number, mitochondrial protein levels and the expression of transcription factors involved in mitochondrial biogenesis, including PPAR-γ coactivator-1α (PGC-1α), Sirtuin 3 (Sirt3), mitochondrial transcription factor A (Tfam) and nuclear related factor 1 (Nrf1). These changes were accompanied by an increase in oxygen consumption and in the expression of genes involved in fatty acid oxidation and antioxidant enzymes in 3T3-L1 adipocytes, including nebivolol-induced endothelial nitric oxide synthase (eNOS), as well as an increase in the formation of cyclic guanosine monophosphate (cGMP). Pretreatment with NG-nitro-L-arginine methyl ester (l-NAME) attenuated nebivolol-induced mitochondrial biogenesis, as did the soluble guanylate cyclase inhibitor, ODQ. Treatment with nebivolol and β3-AR blocker SR59230A markedly attenuated PGC-1α, Sirt3 and manganese superoxide dismutase (MnSOD) protein levels in comparison to treatment with nebivolol alone. These data indicate that the mitochondrial synthesis and metabolism in adipocytes that is promoted by nebivolol is primarily mediated through the eNOS/cGMP-dependent pathway and is initiated by the activation of β3-AR receptors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Adipogenesis stimulates the nuclear localization of EWS with an increase in its O-GlcNAc glycosylation in 3T3-L1 cells

Highlights: • The majority of EWS localizes stably in the cytosol in 3T3-L1 preadipocytes. • Adipogenic stimuli induce the nuclear localization of EWS. • Adipogenesis promotes O-GlcNAcylation of EWS. • O-GlcNAcylation stimulates the recruitment of EWS to the nuclear periphery. - Abstract: Although the Ewing sarcoma (EWS) proto-oncoprotein is found in the nucleus and cytosol and is associated with the cell membrane, the regulatory mechanisms of its subcellular localization are still unclear. Here we found that adipogenic stimuli induce the nuclear localization of EWS in 3T3-L1 cells. Tyrosine phosphorylation in the C-terminal PY-nuclear localization signal of EWS was negative throughout adipogenesis. Instead, an adipogenesis-dependent increase in O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of EWS was observed. Pharmacological inactivation of O-GlcNAcase in preadipocytes promoted perinuclear localization of EWS. Our findings suggest that the nuclear localization of EWS is partly regulated by the glycosylation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increased adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. - Highlights: • Most LA-derived fatty acids from gut lactic acid bacteria potently activated PPARα. • Among tested fatty acids, KetoA and KetoC significantly activated PPARγ. • KetoA induced adipocyte differentiation via the activation of PPARγ. • KetoA enhanced adiponectin production and glucose uptake during adipogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay

In mouse testes, spermatogonial stem cells (SSCs), a subpopulation of GFRα1 (GDNF family receptor-α1)-positive spermatogonia, are widely distributed along the convoluted seminiferous tubules. The proliferation and differentiation of the SSCs are regulated in part by local expression of GDNF (glial cell-derived neurotorphic factor), one of major niche factors for SSCs. However, the in vivo dynamics of the GDNF-stimulated GFRα1-positive spermatogonia remains unclear. Here, we developed a simple method for transplanting DiI-labeled and GDNF-soaked beads into the mouse testicular interstitium. By using this method, we examined the dynamics of GFRα1-positive spermatogonia in the tubular walls close to the transplanted GDNF-soaked beads. The bead-derived GDNF signals were able to induce the stratified aggregate formation of GFRα1-positive undifferentiated spermatogonia by day 3 post-transplantation. Each aggregate consisted of tightly compacted A{sub single} and marginal A{sub paired}–A{sub aligned} GFRα1-positive spermatogonia and was surrounded by A{sub aligned} GFRα1-negative spermatogonia at more advanced stages. These data not only provide in vivo evidence for the inductive roles of GDNF in forming a rapid aggregation of GFRα1-positive spermatogonia but also indicate the usefulness of this in vivo assay system of various growth factors for the stem/progenitor spermatogonia in mammalian spermatogenesis. - Highlights: • A novel bead transplantation assay was developed to examine the in vivo effects of growth factors on spermatogonia. • A rapid aggregation of GFRα1-positive spermatogonia was induced by the transplanted GDNF-soaked beads. • Tightly-compacted A{sub single} and marginal A{sub paired}–A{sub aligned} spermatogonia were formed in each GFRα1-positive aggregate.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19–29 years) and fifteen middle-to older-aged (57–82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (−24% vs. −56%, P < 0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility. - Highlights: • Plasma acylcarnitine profiling reveals metabolic inflexibility in aged individuals. • Time course acylcarnitine profiling is critical to identify metabolic dysfunction. • Acetyl-CoA carboxylase phosphorylation status is related to metabolic dysfunction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates NLRP3 inflammasome-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglial cells

Highlights: • KHG26792 attenuated LPS-induced TNF-α, IL-1β, and IL-6 level in BV2 cells. • KHG26792 attenuated LPS-induced ROS and nitrotyrosine level. • KHG26792 attenuated LPS-induced damage in mitochondrial potential. • KHG26792 attenuated LPS-induced expression of NLRP3, activated caspase-1, and ASC. • KHG26792 attenuated LPS-induced ATP level through P2X7 receptor. The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation. This study investigated the effects of KHG26792 on the inflammasome-mediated signaling pathway in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. KHG26792 significantly attenuated several inflammatory responses including tumor necrosis factor-α, interleukin-1β, interleukin-6, reactive oxygen species, and mitochondrial potential in these cells. KHG26792 also suppressed LPS-induced increase NLRP3, activated caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) levels. Furthermore, KHG26792 successfully blocked LPS-activated adenosine triphosphate (ATP) level, likely through the purinergic receptor P2X ligand-gated ion channel 7 (P2X7) receptor. Our results suggest that the anti-inflammatory functions of KHG26792 may be, at least in part, due to regulation of the P2X7R/NLRP3-mediated signaling pathway during microglial activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Autophagy activation facilitates mechanical stimulation-promoted osteoblast differentiation and ameliorates hindlimb unloading-induced bone loss

Highlights: • Autophagy is activated during mechanical stretching facilitated osteoblast differentiation of BMSCs. • Autophagy activation is essential for mechanical stretching promoted osteoblast differentiation of BMSCs. • Autophagy activation ameliorates hindlimb unloading-induced bone loss by enhancing osteoblast differentiation. Autophagy has been indicated to be involved in regulating bone metabolism. However, little is known about the role of autophagy in mechanical stimulation-influenced osteoblast differentiation and bone formation. In the present study, we first demonstrated that autophagy activation was essential for cyclic mechanical stretching-promoted osteoblast differentiation of bone marrow mesenchymal stem cells. To explore the in vivo role of autophagy in osteoblast differentiation, the hindlimb unloading-induced disuse osteoporosis model was used. Compared to the normal controls, hindlimb unloading led to abundant bone loss as well as lessened autophagy activation of osteoblasts. However, the activation of autophagy by ULK1 overexpression or in the presence of rapamycin significantly increased osteoblast differentiation activity and restored the bone volume. The findings implicate autophagy as a novel mechanosensitive pathway that regulates osteoblast differentiation. The pharmacological activation of autophagy may be an interesting approach for the prevention and treatment of disuse osteoporosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Traditional Chinese medication Tongxinluo attenuates apoptosis in ox-LDL-stimulated macrophages by enhancing Beclin-1-induced autophagy

Highlights: • TXL attenuates ox-LDL-impaired apoptosis in THP-1 macrophages. • TXL attenuates ox-LDL-impaired apoptosis in THP-1 macrophages by enhancing autophagy. • TXL treatment inhibits macrophage apoptosis by enhancing macrophage autophagy in advanced atherosclerotic plaques. • TXL stabilizes atherosclerotic plaques by attenuating macrophage apoptosis and enhancing Beclin-1-induced autophagy. In advanced atherosclerosis, a large number of necrotic core increases plaque vulnerability, which leads to the occurrence of acute atherothrombotic cardiovascular events. Macrophage apoptosis plays an important role in secondary necrosis. The present study aimed to examine and describe the effect of the traditional Chinese medication Tongxinluo (TXL) on macrophage apoptosis in advanced atherosclerotic plaques and to explore its mechanism. By observing the effect of TXL on ox-LDL-stimulated macrophage apoptosis, it was shown that TXL significantly inhibited ox-LDL-induced apoptosis of macrophages by enhancing autophagy. Therapeutic mechanism of TXL included increasing the expression of Beclin-1 and improving the dissociation of Bcl-2-Beclin-1 Complex. Apolipoprotein E knockout (apoE−/−) mice with a high fat diet were divided into four groups: saline group (Saline gavage), low dose TXL group (0.38 g/kg/d, gavage), medium dose TXL group (0.75 g/kg/day, gavage), and high dose TXL group (1.5 g/kg/day, gavage). 4 weeks after carotid-artery surgery, lentiviral of Beclin-1 silencing was injected through the tail vein. TXL treatment significantly reduced macrophage apoptosis dose-dependently and the result was blocked by Beclin-1 silencing. In addition, the increased Lc3b dots by TXL almost localized to macrophages in advanced atherosclerotic plaque. Compared with the same dose of TXL shBeclin-1 group, plaque area and vulnerability index of TXL groups decreased. The anti-apoptosis effects of TXL on atherosclerosis was related to the improvement of autophagy via Beclin-1.

60 APPLIED LIFE SCIENCES↗