Navel orange peel essential oil inhibits the growth and progression of triple negative breast cancer.

BACKGROUND: Triple Negative Breast Cancer (TNBC) is a particular type of breast cancer with the highest mortality rate. Essential oils are concerned more and more as potential anti-cancer drugs. METHODS: TNBC cells were treated with different concentrations of navel orange peel essential oil (NOPEO), and then a variety of  experiments were performed to investigate the changes in the growth and progression of TNBC cells. MTT assay was performed to detect the proliferation of TNBC cells. The changes of cell cycle and apoptosis were analyzed by FACS. In order to explored the migration of TNBC cells, scratch wound assay was carried out. Western blotting and qPCR were used to examine the expression of proteins and mRNA of related genes. Furthermore, RNA-seq was used to analyze the altered genes and explored the possible signal pathway. RESULTS: NOPEO demonstrated dose- and time-dependent suppression of TNBC cell growth. TNBC cells showed an increased percentage of G2/M-phase cells and the protein levels of CyclinB1 and CyclinD1 were decreased after NOPEO treatment. The apoptotic cells were increased in the NOPEO treated TNBC cells. The migration mobility was significantly inhibited by NOPEO. In total, 1376 genes were found to be up-regulated and 1335 genes were down-regulated after NOPEO treatment. According to KEGG and GO pathways, the differentially expressed genes were related to MAPK, Jak/stat and FoxQ signaling pathways. CONCLUSION: This investigation explored the bio-activity and molecular mechanisms of NOPEO against TNBC cells. These results indicated that NOPEO could suppress TNBC growth and migration perhaps via the MAPK and Jak/stat signaling pathways, which may provide theoretical reference for anticancer drug development. NOPEO may be a potential natural product for the chemotherapeutic of TNBC.

Searching for Unconventional Superfluid in Excitons of Monolayer Semiconductors.

It is well known that two-dimensional (2D) bosons in homogeneous space cannot undergo real Bose-Einstein condensation, and the superfluid to normal phase transition is Berezinskii-Kosterlitz-Thouless (BKT) type, associated with vortex-antivortex pair unbinding. Here we point out a 2D bosonic system whose low energy physics goes beyond conventional paradigm of 2D homogeneous bosons, i.e., intralayer excitons in monolayer transition metal dichalcogenides. With intrinsic valley-orbit coupling and valley Zeeman energy, exciton dispersion becomes linear at small momentum, giving rise to a series of novel features. The critical temperature of Bose-Einstein condensation of these excitons is nonzero, suggesting true long-range order in 2D homogeneous system. The dispersion of Goldstone mode at long wavelength has the form ϵ(q)∼sqrt[q], in contrast to conventional linear phonon spectrum. The vortex energy deviates from the usual logarithmic form with respect to system size, but instead has an additional linear term. Superfluid to normal phase transition is no longer BKT type for system size beyond a characteristic scale, without discontinuous jump in superfluid density. With the recent experimental progress on exciton fluid at thermal equilibrium in monolayer semiconductors, our work points out an experimentally accessible system to search for unconventional 2D superfluids beyond BKT paradigm.

Emerging novel targets for nonalcoholic fatty liver disease treatment: Evidence from recent basic studies.

Nonalcoholic fatty liver disease (NAFLD), a leading chronic disease worldwide, affects approximately a quarter of the global population. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD and is more likely to progress to liver fibrosis than simple steatosis. NASH is also identified as the most rapidly growing cause of hepatocellular carcinoma. Although in the past decade, several phase II/III clinical trials have shown promising results in the use of novel drugs targeting lipid synthase, farnesoid X receptor signaling, peroxisome proliferator-activated receptor signaling, hepatocellular injury, and inflammatory signaling, proven pharmaceutical agents to treat NASH are still lacking. Thus, continuous exploration of the mechanism underlying the pathogenesis of NAFLD and the identification of novel therapeutic targets remain urgent tasks in the field. In the current review, we summarize studies reported in recent years that not only provide new insights into the mechanisms of NAFLD development but also explore the possibility of treating NAFLD by targeting newly identified signaling pathways. We also discuss evidence focusing on the intrahepatic targets involved in the pathogenesis of NAFLD as well as extrahepatic targets affecting liver metabolism and function.

Temperature-Dependent Decay of Quasi-Two-Dimensional Vortices across the BCS-BEC Crossover.

We systematically study the decay of quasi-two-dimensional vortices in an oblate strongly interacting Fermi gas over a wide interaction range and observe that, as the system temperature is lowered, the vortex lifetime increases in the Bose-Einstein condensate (BEC) regime but decreases at unitarity and in the Bardeen-Cooper-Schrieffer (BCS) regime. The observations can be qualitatively captured by a phenomenological model simply involving diffusion and two-body collisional loss, in which the vortex lifetime is mostly determined by the slower process of the two. In particular, the counterintuitive vortex decay in the BCS regime can be interpreted by considering the competition between the temperature dependence of the vortex annihilation rate and that of unpaired fermions. Our results suggest a competing mechanism for the complex vortex decay dynamics in the BCS-BEC crossover for the fermionic superfluids.

[Low temperature exposure increases IL-6 expression in skeletal muscle cells].

The shivering and nonshivering thermogenesis in skeletal muscles is important for maintaining body temperature in a cold environment. In addition to nervous-humoral regulation, adipose tissue was demonstrated to directly respond to cold in a cell-autonomous manner to produce heat. However, whether skeletal muscle can directly respond to low temperature in an autoregulatory manner is unknown. Transient receptor potential (TRP) channels TRPM8 and TRPA1 are two important cold sensors. In the current study, we found TRPM8 was expressed in mouse skeletal muscle tissue and C2C12 myotubes by RT-PCR. After exposure to 33 °C for 6 h, the gene expression pattern of C2C12 myotubes was significantly changed which was evidenced by RNA-sequencing. KEGG-Pathway enrichment analysis of these differentially expressed genes showed that low temperature changed several important signaling pathways, such as IL-17, TNFα, MAPK, FoxO, Hedgehog, Hippo, Toll-like receptor, Notch, and Wnt signaling pathways. Protein-protein interaction network analysis revealed that IL-6 gene was a key gene which was directly affected by low temperature in skeletal muscle cells. In addition, both mRNA and protein levels of IL-6 were increased by 33 °C exposure in C2C12 myotubes. In conclusion, our findings demonstrated that skeletal muscle cells could directly respond to low temperature, characterized by upregulated expression of IL-6 in skeletal muscle cells.

Percolation of the two-dimensional XY model in the flow representation.

We simulate the two-dimensional XY model in the flow representation by a worm-type algorithm, up to linear system size L=4096, and study the geometric properties of the flow configurations. As the coupling strength K increases, we observe that the system undergoes a percolation transition K_{perc} from a disordered phase consisting of small clusters into an ordered phase containing a giant percolating cluster. Namely, in the low-temperature phase, there exhibits a long-ranged order regarding the flow connectivity, in contrast to the quasi-long-range order associated with spin properties. Near K_{perc}, the scaling behavior of geometric observables is well described by the standard finite-size scaling ansatz for a second-order phase transition. The estimated percolation threshold K_{perc}=1.1053(4) is close to but obviously smaller than the Berezinskii-Kosterlitz-Thouless (BKT) transition point K_{BKT}=1.1193(10), which is determined from the magnetic susceptibility and the superfluid density. Various interesting questions arise from these unconventional observations, and their solutions would shed light on a variety of classical and quantum systems of BKT phase transitions.

The Chemical Compositions, and Antibacterial and Antioxidant Activities of Four Types of Citrus Essential Oils.

Nanfeng mandarins (Citrus reticulata Blanco cv. Kinokuni), Xunwu mandarins (Citrus reticulata Blanco), Yangshuo kumquats (Citrus japonica Thunb) and physiologically dropped navel oranges (Citrus sinensis Osbeck cv. Newhall) were used as materials to extract peel essential oils (EOs) via hydrodistillation. The chemical composition, and antibacterial and antioxidant activities of the EOs were investigated. GC-MS analysis showed that monoterpene hydrocarbons were the major components and limonene was the predominate compound for all citrus EOs. The antibacterial testing of EOs against five different bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium) was carried out using the filter paper method and the broth microdilution method. Kumquat EO had the best inhibitory effect on B. subtilis, E. coli and S. typhimurium with MIC (minimum inhibitory concentration) values of 1.56, 1.56 and 6.25 µL/mL, respectively. All citrus EOs showed the antioxidant activity of scavenging DPPH and ABTS free radicals in a dose-dependent manner. Nanfeng mandarin EO presented the best antioxidant activity, with IC50 values of 15.20 mg/mL for the DPPH assay and 0.80 mg/mL for the ABTS assay. The results also showed that the antibacterial activities of EOs might not be related to their antioxidant activities.

Universal Dynamical Scaling of Quasi-Two-Dimensional Vortices in a Strongly Interacting Fermionic Superfluid.

Vortices play a leading role in many fascinating quantum phenomena. Here we generate a large number of vortices by thermally quenching a fermionic superfluid of ^{6}Li atoms in an oblate optical trap and study their annihilation dynamics and spatial distribution. Over a wide interaction range from the attractive to the repulsive side across the Feshbach resonance, these quasi-two-dimensional vortices are observed to follow algebraic scaling laws both in time and space, having exponents consistent with the two-dimensional universality. We further simulate the classical XY model on the square lattice by a Glauber dynamics and find good agreement between the numerical and experimental behaviors. Our work provides a direct demonstration of the universal 2D vortex dynamics.

Characterization of Volatile Organic Compounds of Healthy and Huanglongbing-Infected Navel Orange and Pomelo Leaves by HS-GC-IMS.

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the only natural vector of bacteria responsible for Huanglongbing (HLB), a worldwide destructive disease of citrus. ACP reproduces and develops only on the young leaves of its rutaceous host plants. Olfactory stimuli emitted by young leaves may play an important role in ACP control and HLB detection. In this study, volatile organic compounds (VOCs) from healthy and HLB-infected young leaves of navel orange and pomelo were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 36 compounds (including dimers or polymers) were identified and quantified from orange and 10 from pomelo leaves. Some compounds showed significant differences in signal intensity between healthy and HLB-infected leaves and may constitute possible indicators for HLB infection. Principal component analysis (PCA) clearly discriminated healthy and HLB-infected leaves in both orange and pomelo. HS-GC-IMS was an effective method to identify VOCs from leaves. This study may help develop new methods for detection of HLB or find new attractants or repellents of ACP for prevention of HLB.

Cooling and entangling ultracold atoms in optical lattices.

Scalable, coherent many-body systems can enable the realization of previously unexplored quantum phases and have the potential to exponentially speed up information processing. Thermal fluctuations are negligible and quantum effects govern the behavior of such systems with extremely low temperature. We report the cooling of a quantum simulator with 10,000 atoms and mass production of high-fidelity entangled pairs. In a two-dimensional plane, we cool Mott insulator samples by immersing them into removable superfluid reservoirs, achieving an entropy per particle of [Formula: see text] The atoms are then rearranged into a two-dimensional lattice free of defects. We further demonstrate a two-qubit gate with a fidelity of 0.993 ± 0.001 for entangling 1250 atom pairs. Our results offer a setting for exploring low-energy many-body phases and may enable the creation of large-scale entanglement.

Chemical Composition, Antimicrobial, Antioxidant, and Antiproliferative Properties of Grapefruit Essential Oil Prepared by Molecular Distillation.

Grapefruit essential oil has been proven to have wide range of bioactivities. However, bioactivity of its molecular distillate has not been well studied. In this study, a light phase oil was obtained by molecular distillation from cold-pressed grapefruit essential oil and GC-MS was used to identify its chemical composition. The antimicrobial activity of the light phase oil was tested by filter paper diffusion method, and the anticancer activity was determined by the Cell Counting Kit-8 (CCK-8) assay. Twenty-four components were detected with a total relative content of 99.74%, including 97.48% of terpenes and 1.66% of oxygenated terpenes. The light phase oil had the best antimicrobial effect on Bacillus subtilis, followed by Escherichia coli, Staphylococcus aureus and Salmonellaty phimurium. DPPH and ABTS assays demonstrated that the light phase oil had good antioxidant activity. The CCK-8 assay of cell proliferation showed that the light phase oil had a good inhibitory effect on the proliferation of HepG2 liver cancer cells and HCT116 colon cancer cells.

Extraction of 'Gannanzao' Orange Peel Essential Oil by Response Surface Methodology and its Effect on Cancer Cell Proliferation and Migration.

The essential oil of 'Gannanzao' orange peel was extracted by hydrodistillation, and the extraction conditions were optimized by Box⁻Behnken response surface methodology. The components of essential oil were analyzed by GC-MS. Thirty-nine different components were detected, accounting for 99.59% of the total oil. Limonene (88.07%) was the prominent component. The optimal extraction conditions were as follows: liquid material ratio of 8.4:1 (mL/g), sodium chloride concentration of 5.3%, and distillation time of 3.5 h. The Cell Counting Kit-8 assay showed that 'Gannanzao' orange peel essential oil had good dose-dependent inhibition effect on the proliferation of HepG2 hepatoma cells and HCT116 colorectal cancer cells. When the concentration of the essential oil was 0.6 µL/mL or higher, the viability rate of both cancer cells became lower than 13.0%. The transwell assay indicated the essential oil can inhibit migration of both cancer cells at the concentration of 0.3 µL/mL.

Uptake of soil-applied thiamethoxam in orange and its effect against Asian citrus psyllid in different seasons.

BACKGROUND: Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is an important pest of citrus worldwide because it transmits the bacteria causing huanglongbing (HLB). We investigated the effects and persistence of two soil application rates of thiamethoxam on ACP populations in two flushing seasons in the field. Thiamethoxam and clothianidin residues in the fruit were detected to evaluate food safety. RESULTS: Soil application of 50% thiamethoxam water-dispersible granules at concentrations of 4 and 10 g tree-1 significantly decreased ACP populations, and there was a positive correlation between control efficacy and the persistence of thiamethoxam and clothianidin in leaves, providing longer-term protection for up to 90 days in the fall compared with 60 days in the spring. Higher thiamethoxam and clothianidin amounts were observed in new leaves than in old leaves. Thiamethoxam and clothianidin residues at a high rate in fruit were 0.012 and 0.010 mg kg-1 at harvest, respectively, and neither insecticides was detectable at low rates. CONCLUSIONS: These results demonstrate that soil-applied thiamethoxam plays a role in defending ACP, and provides an extended period of control efficacy. This knowledge could provide a reference for the control of ACP by soil application of thiamethoxam to reduce HLB spread. © 2018 Society of Chemical Industry.

Chemical composition and antimicrobial activity of Gannan navel orange (Citrus sinensis Osbeck cv. Newhall) peel essential oils.

The present investigation reported the chemical composition of cold pressed Gannan navel orange peel essential oil (EO) and its molecular distillation fraction (light phase EO), and examined their antimicrobial activity against spoiling and pathogenic microorganisms. Gas chromatography-mass spectrometry analysis identified 27 and 20 different chemical constituents in cold pressed EO and light phase EO, respectively. Limonene was the major constituent, accounting for 85.32% of cold pressed EO and 60.44% of light phase EO. Both EOs and some of their constituents showed good antimicrobial activity. Compared to cold pressed EO, light phase EO exhibited the better antimicrobial activity under weak acidic and neutral conditions. The light phase EO presented a higher antimicrobial activity after thermo-treatment at 60-100°C for 20 min than cold pressed EO. These results demonstrated that light phase EO had a potential to be used as a novel antimicrobial agent for food preservation and food processing.

Dynamics of Topological Excitations in a Model Quantum Spin Ice.

We study the quantum spin dynamics of a frustrated XXZ model on a pyrochlore lattice by using large-scale quantum Monte Carlo simulation and stochastic analytic continuation. In the low-temperature quantum spin ice regime, we observe signatures of coherent photon and spinon excitations in the dynamic spin structure factor. As the temperature rises to the classical spin ice regime, the photon disappears from the dynamic spin structure factor, whereas the dynamics of the spinon remain coherent in a broad temperature window. Our results provide experimentally relevant, quantitative information for the ongoing pursuit of quantum spin ice materials.

Antioxidant and Anticancer Activities of Essential Oil from Gannan Navel Orange Peel.

China is one of the leading producers of citrus in the world. Gannan in Jiangxi Province is the top navel orange producing area in China. In the present study, an essential oil was prepared by cold pressing of Gannan navel orange peel followed by molecular distillation. Its chemical composition was analyzed by GC-MS. Twenty four constituents were identified, representing 97.9% of the total oil. The predominant constituent was limonene (74.6%). The anticancer activities of this orange essential oil, as well as some of its major constituents, were investigated by MTT assay. This essential oil showed a positive effect on the inhibition of the proliferation of a human lung cancer cell line A549 and prostate cancer cell line 22RV-1. Some of the oil constituents displayed high anticancer potential and deserve further study.

Fumigant Activity of Sweet Orange Essential Oil Fractions Against Red Imported Fire Ants (Hymenoptera: Formicidae).

Sweet orange oil fractions were prepared by molecular distillation of cold-pressed orange oil from sample A (Citrus sinensis (L.) 'Hamlin' from America) and sample B (Citrus sinensis Osbeck 'Newhall' from China) respectively, and their fumigant activities against medium workers of red imported fire ants (Solenopsis invicta Buren) were investigated. The volatile composition of the orange oil fractions was identified and quantified using GC-MS. Fractions from sample A (A1, A2, and A3) contained 23, 37, and 48 chemical constituents, and fractions from sample B (B1, B2, and B3) contained 18, 29, and 26 chemical constituents, respectively. Monoterpenes were the most abundant components, accounting for 73.56% to 94.86% of total orange oil fractions, among which D-limonene (65.28-80.18%), ß-pinene (1.71-5.58%), 3-carene (0.41-4.01%), ß-phellandrene (0.58-2.10%), and linalool (0.31-2.20%) were major constituents. Fumigant bioassay indicated that all orange oil fractions exerted good fumigant toxicity against workers of fire ants at 3, 5, 10, and 20 mg/centrifuge tubes, and B1 had the strongest insecticidal potential, followed by A1, B2, A2, B3, and A3. The fractions composed of more high volatile molecules (A1 and B1) showed greater fumigant effects than others. Compounds linalool and D-limonene, which were the constituents of the orange oil, exhibited excellent fumigant toxicity against red imported fire ant workers. Linalool killed red imported fire ant workers completely at 5, 10, and 20 mg/tube after 8 h of treatment, and D-limonene induced >86% mortality at 8 h of exposure.

Liver X receptor α induces 17ß-hydroxysteroid dehydrogenase-13 expression through SREBP-1c.

Liver X receptors, including LXRα and LXRß, are known to be master regulators of liver lipid metabolism. Activation of LXRα increases hepatic lipid storage in lipid droplets (LDs). 17ß-Hydroxysteroid dehydrogenase-13 (17ß-HSD13), a recently identified liver-specific LD-associated protein, has been reported to be involved in the development of nonalcoholic fatty liver disease. However, little is known about its transcriptional regulation. In the present study, we aimed at determining whether 17ß-HSD13 gene transcription is controlled by LXRs. We found that treatment with T0901317, a nonspecific LXR agonist, increased both 17ß-HSD13 mRNA and protein levels in cultured hepatocytes. It also significantly upregulated hepatic 17ß-HSD13 expression in wild-type (WT) and LXRß-/- mice but not in LXRα-/- mice. Basal expression of 17ß-HSD13 in the livers of LXRα-/- mice was lower than that in the livers of WT and LXRß-/- mice. Moreover, induction of hepatic 17ß-HSD13 expression by T0901317 was almost completely abolished in SREBP-1c-/- mice. Bioinformatics analysis revealed a consensus sterol regulatory element (SRE)-binding site in the promoter region of the 17ß-HSD13 gene. A 17ß-HSD13 gene promoter-driven luciferase reporter and ChIP assays further confirmed that the 17ß-HSD13 gene was under direct control of SREBP-1c. Collectively, these findings demonstrate that LXRα activation induces 17ß-HSD13 expression in a SREBP-1c-dependent manner. 17ß-HSD13 may be involved in the development of LXRα-mediated fatty liver.

Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue.

Among the four prostaglandin E2 receptors, EP3 receptor is the one most abundantly expressed in white adipose tissue (WAT). The mouse EP3 gene gives rise to three isoforms, namely EP3α, EP3ß, and EP3γ, which differ only at their C-terminal tails. To date, functions of EP3 receptor and its isoforms in WAT remain incompletely characterized. In this study, we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice. Genetic ablation of three EP3 receptor isoforms (EP3-/- mice) or EP3α and EP3γ isoforms with EP3ß intact (EP3ß mice) led to an obese phenotype with increased food intake, decreased motor activity, reduced insulin sensitivity, and elevated serum triglycerides. Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγ pathway, increased adipogenesis may contribute to obesity in EP3-/- and EP3ß mice. Moreover, both EP3-/- and EP3ß mice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway. Taken together, our findings suggest that EP3 receptor and its α and γ isoforms are involved in both adipogenesis and lipolysis and influence food intake, serum lipid levels, and insulin sensitivity.

Metabolomic analysis revealed the role of DNA methylation in the balance of arachidonic acid metabolism and endothelial activation.

Arachidonic acid (AA) metabolism plays an important role in vascular homeostasis. We reported that DNA hypomethylation of EPHX2 induced a pro-inflammatory response in vascular endothelial cells (ECs). However, the change in the whole AA metabolism by DNA methylation is still unknown. Using a metabolomic approach, we investigated the effect of DNA methylation on the balance of AA metabolism and the underlying mechanism. ECs were treated with a DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AZA), and AA metabolic profiles were analyzed. Levels of prostaglandin D2 (PGD2) and thromboxane B2 (TXB2), metabolites in the cyclooxygenase (COX) pathway, were significantly increased by 5-AZA treatment in ECs resulting from the induction of PGD2 synthase (PTGDS) and thromboxane A synthase 1 (TBXAS1) expression by DNA hypomethylation. This phenomenon was also observed in liver and kidney cell lines, indicating a universal mechanism. Pathophysiologically, homocysteine, known to cause DNA demethylation, induced a similar pattern of the change of AA metabolism. Furthermore, 5-AZA activated ECs, as evidenced by the upregulation of adhesion molecules. Indomethacin, a COX inhibitor, reversed the effects of 5-AZA on the levels of PGD2 and TXB2, EC activation and monocyte adhesion. In vivo, the plasma levels of PGD2 and TXB2 and the expression of In vivo PTGDS and TBXAS1 as well as adhesion molecules were increased in the aorta of the mice injected with 5-AZA. In conclusion, using a metabolomic approach, our study uncovered that DNA demethylation increased AA metabolites PGD2 and TXB2 by upregulating the expression of the corresponding enzymes, which might contribute to the DNA hypomethylation-induced endothelial activation.