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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 667 records · Page 37

OSIRIS-REx Contamination Control Strategy and Implementation

OSIRIS-REx will return pristine samples of carbonaceous asteroid Bennu. This manuscript describes how pristine was defined based on expectations of Bennu and on a realistic understanding of what is achievable with a constrained schedule and budget, and how that definition flowed to requirements and implementation. To return a pristine sample, the OSIRIS-REx spacecraft sampling hardware was maintained at Level 100 A/2 and less than 180 nanograms per square centimeter of amino acids and hydrazine on the sampler head through precision cleaning, control of materials, and vigilance. Contamination is further characterized via witness material exposed to the spacecraft assembly and testing environment as well as in space. This characterization provided knowledge of the expected background and will be used in conjunction with archived spacecraft components for comparison with the samples when they are delivered to Earth for analysis. Most of all, the cleanliness of the OSIRIS-REx spacecraft was achieved through communication between scientists, engineers, managers, and technicians.

Dworkin, J. P.↗

The CAESAR New Frontiers Mission: Comet Surface Sample Acquisition and Preservation

NASA recently selected the Comet Astrobiology Exploration Sample Return (CAESAR) mission for Phase A study in the New Frontiers Program. This mission will acquire and return to Earth for laboratory analysis at least 80 g of surface material from the nucleus of comet 67P/Churyumov-Gerasimenko (hereafter 67P). CAESAR will characterize the surface region sampled, preserve the sample in a pristine state, and return evolved volatiles by capturing them in a separate gas reservoir. The system protects both volatile and non-volatile components from contamination or alteration thatwould hamper their scientific analysis. Laboratory analyses of comet samples provide unparalleled knowledge about the presolar history through the initial stages of planet formation to the origin of life.

CAESAR↗

The CAESAR New Frontiers Mission: 1. Expected Nature of the Returned Comet Sample

Comets are time capsules from the birth of our Solar System that record pre-solar history, the initial stages of planet formation, and the sources of prebiotic organics and volatiles for the origin of life. These capsules can only be opened in laboratories on Earth. CAESAR (Comet Astrobiology Exploration Sample Return)’s sample analysis objectives are to understand the nature of Solar System starting materials and how these components came together to form planets and give rise to life. Examination of these comet nucleus surface samples in laboratories around the world will also provide ground truth to remote observations of the innumerable icy bodies of the Solar System.

Lauretta, D. S.↗

Synthesis and anticancer effects of α-lipoic ester of alloxanthoxyletin

Upon analyzing the structure-activity relationship, it was found that coumarin-based derivatives exerted cytotoxic and antitumor activity. In the present study a new ester of α-lipoic acid and derivative of alloxanthoxyletin (LAA) was synthesized and evaluated for its anticancer activity. The structure of this new compound was confirmed by {sup 1}H NMR, {sup 13}C NMR, and HRMS spectroscopic analyses. Both, the cytotoxicity and the migration tests showed that human melanoma cells (HTB-140) and human lung cancer cells (A549) were more sensitive to LAA exposure than human normal keratinocytes (HaCaT). Moreover, LAA induced significant HTB-140 and A549 apoptosis, as evidenced by V-FITC/7-AAD flow cytometry analysis. Preincubation of the HTB-140 and A549 cells with LAA increased a sensitivity of tumor cells to a drug-induced cell death. Significantly lower expression of IL-6 mRNA was observed in A549 and HTB-140 cells which were pre-incubated with LAA and then treated with doxorubicin as compared to the cells pre-incubated with LAA and then treated with cisplatin. The results suggest that the newly synthetized LAA is compound with anticancer activity promising for potential applications, but further studies are needed to gain more insight into the mechanism of action of tested derivative.

60 APPLIED LIFE SCIENCES↗

Zunyimycin C inhibits the proliferation of lung cancer cells by inducing apoptosis through an AKT-related mechanism

Objective: Zunyimycin C is a novel halogenated type II polyketide derived from the fermentation product of the Streptomyces species with notable antibiotic activity. However, it is still unclear whether zunyimycin C could inhibit the activity of cancer cells. In this study, human lung adenocarcinoma cell line A549, the large-cell lung cancer cell line NCI-H460 and the non-small-cell lung cancer cell line NCI-H1299 were employed to determine the in vitro anticancer properties of zunyimycin C and underlying molecular mechanisms. Materials and methods: The cellular viability and proliferative properties of lung cancer cells were investigated using the Cell Counting Kit-8 and colony formation assay, respectively. The mRNA expression of apoptotic genes related to lung cancer was studied using reverse-transcription polymerase chain reaction. The apoptotic ratio was measured through flow cytometry. The protein expression was visualized via western blotting using specific antibodies. Results: Zunyimycin C could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. The expression levels of apoptosis-related proteins (i.e., BAX, cleaved-caspase-3, and cleaved-caspase-9) were increased compared with the control group. However, the levels of Bcl-2 and phosphorylated AKT were decreased by administration by zunyimycin C. Conclusions: Collectively, these results implied that zunyimycin C could inhibit cell proliferation and induce apoptosis via AKT phosphorylation.

60 APPLIED LIFE SCIENCES↗

Reception of Sex Steroid Hormones in Thyroid Papillary Cancer Tissue and Relationship with Expression and Content of Transcription Factors Brn-3α and TRIM16

We studied reception of sex steroid hormones in the tissues of thyroid papillary cancer and benign tumor. Enhanced expression of AR and ERβ mRNA reflected malignant tumor growth. Nuclear factors Brn-3α and TRIM16 modulating expression of steroid hormones play an important role in the development of thyroid tumors. It was found that the level of TRIM16 mRNA is associated with the expression of ERβ, which seems to be mediated by its antiestrogen effect.

60 APPLIED LIFE SCIENCES↗

Influence of Magnetite Nanoparticles and Quantum Dots on the Expression of Reference Genes in Peripheral Blood Cells

We studied the influence of magnetite nanoparticles (FeO•Fe{sub 2}O{sub 3}) and quantum dots (CdSe/ZnS coated with mercaptopropionic acid) on the expression of 5 common reference genes (BA, B2M, PPIA, UBC, and YWHAZ) in peripheral blood cells from 20 volunteers by reverse transcription PCR method. The stability of the expression of reference genes varied depending of the cells type and chemical structure of nanoparticles. The level of YWHAZ mRNA after exposure by nanoparticles demonstrated highest stability in lymphocytes, neutrophils, and monocytes. Stability of YWHAZ expression was confirmed by Western blotting. Our findings suggest that YWHAZ is the most suitable as the reference gene.

60 APPLIED LIFE SCIENCES↗

Direct Estimation of Parameters in ODE Models Using WENDy: Weak-Form Estimation of Nonlinear Dynamics

Abstract We introduce the Weak-form Estimation of Nonlinear Dynamics (WENDy) method for estimating model parameters for non-linear systems of ODEs. Without relying on any numerical differential equation solvers, WENDy computes accurate estimates and is robust to large (biologically relevant) levels of measurement noise. For low dimensional systems with modest amounts of data, WENDy is competitive with conventional forward solver-based nonlinear least squares methods in terms of speed and accuracy. For both higher dimensional systems and stiff systems, WENDy is typically both faster (often by orders of magnitude) and more accurate than forward solver-based approaches. The core mathematical idea involves an efficient conversion of the strong form representation of a model to its weak form, and then solving a regression problem to perform parameter inference. The core statistical idea rests on the Errors-In-Variables framework, which necessitates the use of the iteratively reweighted least squares algorithm. Further improvements are obtained by using orthonormal test functions, created from a set of $$C^{\infty }$$ C ∞ bump functions of varying support sizes.We demonstrate the high robustness and computational efficiency by applying WENDy to estimate parameters in some common models from population biology, neuroscience, and biochemistry, including logistic growth, Lotka-Volterra, FitzHugh-Nagumo, Hindmarsh-Rose, and a Protein Transduction Benchmark model. Software and code for reproducing the examples is available at https://github.com/MathBioCU/WENDy .

97 MATHEMATICS AND COMPUTING↗

Therapeutic Potential of DNAzyme Loaded on Chitosan/Cyclodextrin Nanoparticle to Recovery of Chemosensitivity in the MCF-7 Cell Line

Commonly, acquired resistances to anticancer drug are mediated by overexpression of a membrane-associated protein that encode via multi-drug resistance gene-1 (MDR1). Herein, the mRNA-cleaving DNAzyme that targets the mRNA of MDR1 gene in doxorubicin-resistant breast cancer cell line (MCF-7/DR) loaded on the chitosan β-cyclodextrin complexes was used as a tropical agent. Chitosan/β-cyclodextrin complexes were used to deliver DNAzymes into cancer cells. Determination of the physicochemical characteristics of the particles was done by photon correlation spectroscopy and scanning electron microscopy. The encapsulation efficiency of the complexes was tested by using gel retardation assay. Positively charged nanoparticles interacted with DNAzyme that could perform as an efficient DNAzyme transfection system. The rationale usage of this platform is to sensitize MCF-7/DR to doxorubicin by downregulating the drug-resistance gene MDR1. Results demonstrated a downregulation of MDR1 mRNAs in MCF-7/DR/DNZ by real-time PCR, compared to the MCF-7/DR as control. WST1 assay showed the 22-fold decrease in drug resistance on treated cells 24 h after transfection. Results showed the intracellular accumulation of Rh123 increased in the treated cells with DNAzyme. Results suggested a potential platform in association with chemotherapy drug for cancer therapy and indicated extremely efficient at delivery of DNAzyme in restoring chemosensitivity.

60 APPLIED LIFE SCIENCES↗

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↗

In Vitro Wound Healing Activity of Wheat-Derived Nanovesicles

Triticum aestivum plant extracts are often used as a natural healer in traditional medicine but which particles mainly have role in these processes are not scientifically proven. In other words, no attempts have been made to investigate the effects of wheat exosomes in regenerative medicine applications or drug development up to now. The current study was first time performed to demonstrate the activity of wheat exosomes in wound healing process using in vitro approaches. Although its fundamental wound healing process remains a mystery, in the current study, the efficiency of wheat grass juice–derived exosomes on cell viability and migration was examined. Increasing concentrations up to 200 μg/mL of the wheat exosome have yielded astonishing proliferative and migratory effects on endothelial, epithelial, and dermal fibroblast cells. RT-PCR analysis also showed collagen type I; mRNA levels were approximately twofold higher in expression after treating with 200 μg/mL wheat exosome. Additionally, Annexin V staining of apoptotic cells accompanied with the cell cycle analysis resulted with the reduction of the apoptotic cell number with no dispersion to the cell cycle analysis while plant exosomes have also increased tube-like structure formation of the endothelial cells. All in all, this research suggests a brand-new opening for skin wound healing therapy strategy by using wheat-derived exosomes due to its proliferative and migratory characteristics. Plant exosomes require a further research both clinically and in in vivo for wound healing drug development. Moreover, plant exosome therapy strategies would be safer and economical alternative for clinical wound healing.

60 APPLIED LIFE SCIENCES↗

Withaferin A Protects Against High-Fat Diet–Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance

Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.

60 APPLIED LIFE SCIENCES↗

Inhibitory Effects of Vanadium-Binding Proteins Purified from the Sea Squirt Halocynthia roretzi on Adipogenesis in 3T3-L1 Adipocytes

The inhibitory effects of vanadium-binding proteins (VBPs) from the blood plasma and the intestine of sea squirt on adipogenesis in 3T3-L1 adipocytes were examined. 3T3L-1 cells treated with VBP {sub blood plasma} decreased markedly the lipid content in maturing pre-adipocytes in a dose-dependent manner, whereas VBP {sub intestine} did not show significant effects on lipid accumulation. Both VBPs did not have significant effect on cell viability. In order to demonstrate the anti-adipogenic effects of VBP {sub blood plasma}, the expressions of several adipogenic transcription factors and enzymes were investigated by Reverse Transcriptase-Polymerase Chain Reaction. VBP {sub blood plasma} down-regulated the expressions of transcription factors; PPAR-γ, C/EBP-α, SREBP1, and FAS, but did not have significant effects on the expressions of lipolytic enzymes; HSL and LPL. Both the crude and purified VBPs significantly increased the mRNA levels of Wnt10b, FZ1, LRP6, and β-catenin, while decreased the expression of GSK-3β. Hence, VBP {sub blood plasma} inhibited adipogenesis by activating WNT/β-catenin pathway via the activation of Wnt10b. Based on the findings, VBP {sub blood plasma} decreased lipid accumulation which was mediated by decreasing adipogenesis, not by lipolysis. Therefore, VBP {sub blood plasma} could be used to treat obesity.

60 APPLIED LIFE SCIENCES↗

Therapeutic effects of moxibustion simultaneously targeting Nrf2 and NF-κB in diabetic peripheral neuropathy

Moxibustion is the main alternative medicine treatment that has been beneficial to diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying protective mechanism of moxibustion against neuroinflammation remains unclear. We hypothesized that moxibustion treats DPN by regulating the balance of nuclear factor-2 erythroid-related factor-2 (Nrf2)-nuclear factor-kappa light chain enhancer of B cells (NF-кB). In vivo, diabetes was induced in rats by injecting streptozotocin (STZ; 60 mg/kg; i.p.). Moxibustion was then applied to “Zusanli” (ST 36), “Guanyuan” (BL 26), and “Yishu” (EX-B 3) acupuncture points. Nerve conduction was detected. Serum interleukin (IL)-1β, IL-6, and IL-8 levels were determined through enzyme-linked immunosorbent assay. NF-κB and Nrf2 proteins were examined through immunoblot analysis. The mRNA of NF-κB and Nrf2 was evaluated through RT-PCR. We found that the conduction velocity and amplitude of the action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by moxibustion treatment. Moxibustion also improved the effect of DPN on other parameters, including ultrastructural changes, NF-κB and Nrf2 expression in the sciatic nerve, and serum IL-1β, IL-6, and IL-8 levels. Our data suggested that moxibustion may alleviate neuroinflammation by inhibiting NF-κB and by activating Nrf2. Moxibustion may also provide therapeutic effects for patients with DPN by simultaneously targeting Nrf2 and NF-κB.

60 APPLIED LIFE SCIENCES↗

Importance of m N{sup 6}-methyladenosine (m{sup 6}A) RNA modification in cancer

RNA methylation, which was identified back in 1970s, has gained remarkable interest in recent years as it was shown to be a reversible modification involved in many cellular processes like mRNA and miRNA processing, mRNA localisation, translation suppression, or activation. These, in turn, affect important bioprocesses such as tissue development, sex determination, and DNA damage response. Important group of proteins are responsible for adding, recognizing, and removing the methyl group to and from the RNA molecules, which are referred as writers, readers, and erasers, respectively. If any of the processes is not strictly controlled, this can cause abnormalities in gene expression, which result in diseases including cancers such as lung, pancreas, glioblastoma, and breast cancer. Mechanisms of RNA methylation and its role in various cancer types and diagnostic methods for RNA methylation are discussed in this article.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Performance of a new system using a one-step nucleic acid amplification assay for detecting lymph node metastases in breast cancer

One-step nucleic acid amplification (OSNA) for CK19 mRNA is an intraoperative diagnostic procedure for detection of lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of a new OSNA system have been developed. As an improvement over a conventional system, the new system can analyze 14 samples per run, evaluate two lymph nodes in ~ 17 min, and reduce inhibition of reactions. This study was aimed at evaluating clinical performance of the new system by comparing it with performance of histopathological analysis and a conventional OSNA system. A total of 150 lymph nodes in 63 breast cancer patients (T1–3) who underwent sentinel lymph node biopsy or axillary lymph node dissection were examined intraoperatively with the new OSNA system, the conventional system, and histopathological analysis. In comparison with histopathological analysis, sensitivity, specificity, and concordance rate of the new system were 93.9, 98.8, and 96.7%, respectively. In comparison with the conventional system, similar corresponding values were obtained: 96.9, 98.8, and 98.0%, respectively. The results show that clinical performance of the new OSNA system is equivalent to that of histopathological diagnosis and the conventional OSNA system. The new system is superior to the conventional one because of processing of a greater number of samples, shorter testing time, and the absence of inhibited reactions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Mechanism of VIPR1 gene regulating human lung adenocarcinoma H1299 cells

The vasoactive intestinal peptide receptor-1(VIPR1) has prominent growth effects on a number of common neoplasms. However, there were contradictions in the effect cross different cancers. We aimed to explore the effect of VIPR1 overexpression on a human lung adenocarcinoma cell line H1299. GEO dataset was used to screen differentially expressed genes in lung adenocarcinoma tissues. The expression of VIPR1 mRNA was determined in the cancer Genome Atlas (TCGA). Immunohistochemical analysis was performed to determine VIPR1 protein expression in lung adenocarcinoma and corresponding adjacent tissues (n = 22). Fluorescence real-time quantitative PCR detected the expression of VIPR1 in human normal lung epithelial cell line BEAS-2B and lung adenocarcinoma cell line H1299. Overexpression strategies were employed to assess functions of VIPR1 expression on several malignant phenotypes in H1299. The expression of VIPR1 was lower in lung adenocarcinoma tissues than that in adjacent tissues. Compared with the normal lung epithelial cells BEAS-2B, VIPR1 was down-regulated in lung cancer cells H1299 (P < 0.05). After the overexpression of VIPR1, we found that VIPR1 significantly inhibited growth, migration, and invasion of H1299 cells (P < 0.05). Our findings point out the tumor suppressor roles of VIPR1 in human LUAD pathogenesis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗