Context:
Graves' orbitopathy (GO) is a disfiguring/distressing, inflammatory autoimmune condition. This intractable problem is caused by expansion of the orbital contents around the eye by excessive ...fat generation (adipogenesis) and overproduction of extracellular matrix components, especially hyaluronan (HA) from preadipocytes/fibroblasts (PFs). Current immunosuppressive/antiinflammatory treatments are largely ineffective and have unpleasant side effects, and a better therapeutic strategy through understanding GO-associated pathological features is needed.
Objective:
Previously we identified depot-specific HA synthase 2 regulation (HAS2; major source of HA), which facilitates orbit-specific HA accumulation during adipogenesis, and targeting phosphatidylinositol-3-kinase/mechanistic target of rapamycin-complex-1 pathways blocked both pathological features. The current study revealed low expression levels of Forkhead box O (FOXOs; critical downstream effectors of phosphatidylinositol-3-kinase) in orbital PFs through adipogenesis compared with sc levels. We aimed to dissect the role of FOXOs in GO pathogenesis to identify nonimmunosuppressive targets for GO treatment.
Design/Setting/Participants:
Human orbital and sc primary PFs were treated with small interfering RNA/chemical inhibitor (AS1842856) of FOXOs or FOXO enhancer trifluoperazine hydrochloride (TFP; Food and Drug Administration approved drug), in serum-free medium for 24 hours, or TFP treatment in adipogenic medium for 15 days.
Main Outcome Measures:
Quantitative PCR was used to measure HAS2 transcripts and the terminal adipogenesis differentiation marker lipoprotein lipase. HA accumulation in the medium was measured by an ELISA.
Results:
Substantially increased or decreased HAS2/HA production was observed by inhibiting (small interfering RNA or chemical inhibitor) or enhancing (TFP) FOXO expression, respectively. TFP treatment is also sufficient to counteract thyrotropin receptor-activated HAS2/HA production and block adipogenesis in orbital PFs.
Conclusions:
FOXOs play a crucial repressor role in the regulation of HAS2/HA production and adipogenesis in orbital PFs. Our data reveal for the first time that resetting GO-associated pathological features through drug-targeted activation of FOXOs could provide a feasible nonimmunosuppressive therapeutic strategy for GO.
We explored arbuscular mycorrhizal fungi (AMF) in the rhizosphere soil under Robinia pseudoacacia L., Leguminosae (black locust), and evaluated the relations between their diversity and soil and ...climatic factors in the semi‐arid Loess Plateau of northwest China. A total of 23 AMF species were identified at six sites. Of these, six belonged to the genus Funneliformis (Glomeraceae), five to Rhizophagus (Glomeraceae), three to Glomus (Glomeraceae), two to Acaulospora (Acaulosporaceae), two to Claroideoglomus (Claroideoglomeraceae), two to Septoglomus (Glomeraceae), one to Ambispora (Ambisporaceae), one to Scutellospora (Gigasporaceae) and one to Sclerocystis (Glomeraceae). The species that occurred in the largest proportion of soil samples were Rhizophagus intraradices (75%) and Funneliformis dimorphicum (66.7%). Soil‐available potassium was positively correlated with mycorrhizal colonization and species richness. Spore density was negatively correlated with soil pH, whereas the Shannon–Wiener diversity index was positively correlated with total potassium. Most of the soil and climatic factors measured affected the AMF indices directly rather than indirectly. The relative abundances of 13 AMF species were strongly affected by precipitation, temperature, total nitrogen, ammonium nitrogen and available potassium. This suggests that AMF species are diverse and Funneliformis was the most common and dominant AMF genus in the rhizosphere soil under black locust in the Loess Plateau. Precipitation directly affected AMF status and diversity in this distinctive semi‐arid ecosystem.
Highlights
Analysis of the effects of soil and climatic factors on mycorrhizal colonization and AMF diversity of black locust.
Improved understanding of AMF communities and their function in soil under black locust.
Precipitation was the strongest direct factor that affected AMF in the semi‐arid region.
Funneliformis was the most common AMF genus in rhizosphere soil under black locust.
Natural orifice transluminal endoscopic surgery (NOTES) has received significant attentions due to its minimal incision trauma compared with traditional multi-port robot assisted surgery. Continuum ...robot can be used in NOTES due to its high flexibility which can adapt to circuitous paths. However, the modeling of continuum robot is complex due to its nonlinear dynamics, especially with uncertain external disturbance. In this letter a hybrid adaptive control framework is proposed, combining offline trained robot inverse kinematics with neural network and online adaptive adjustment of PID controller parameters with another neural network, providing additional driving amount to the robot system to compensate the positioning error caused by external disturbance. Path tracking and point tracking experiments with external load are conducted and the results validate that the proposed hybrid adaptive control framework can compensate uncertain factors such as friction, driving tendon relaxation and external load during robot movement, and obtain relatively high positioning accuracy (maximum absolute error less than 2 mm) with quickresponse.
In laboratories, the parasitism rate of Ostrinia furnacalis (Güenée) (Lepidoptera: Crambidae) eggs by Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) is low; however, efforts to ...control O. furnacalis with T. dendrolimi in the field have been successful. In this study, the effects of the number of attacks by T. dendrolimi against O. furnacalis eggs and diet of O. furnacalis larva on wasp development were investigated. The results indicated that more attacks increased significantly not only the successful parasitism rate of O. furnacalis eggs by T. dendrolimi, but also the percentage of host eggs that failed to develop into either O. furnacalis larvae or T. dendrolimi. Both the size and female proportion of T. dendrolimi offspring decreased as the number of attacks increased. The number of T. dendrolimi eggs laid in per host egg increased significantly as the ratio of wasps to host eggs increased from 1:5 to 3:5. Host diet also significantly affected the developmental time of immaturity and the emergence rate of adults of T. dendrolimi. These results illustrate how inundative releases of T. dendrolimi can successfully control O. furnacalis despite the fact that pest parasitism by the subsequent wasp generation decreases sharply in the field. The suitability of O. furnacalis eggs to T. dendrolimi and the superparasitism effects on offspring of T. dendrolimi are discussed.
One plant genotype displays a resistance phenotype at one development stage but a susceptible reaction to the same pathogen at another stage, which is referred to here as resistance inversion. In ...wheat, Fusarium head blight (FHB)-resistant cv. Sumai3 showed a Fusarium seedling blight (FSB)-susceptible reaction whereas FHB-susceptible cv. Annong8455 exhibited FSB resistance when challenged with a Fusarium asiaticum strain that produces deoxynivalenol (DON). The resistance to FHB and FSB in wheat was closely associated with expression of a plant cytochrome P450 gene in response to FHB pathogens and mycotoxins. Quantitative real-time polymerase chain reaction analyses showed that expression of nine defense-related genes in spikes and seedlings was induced by the fungal infection, in which a massive accumulation of a plant cytochrome P450 gene, CYP709C1, was clearly associated with the resistance reaction in both seedling and spike. The FHB-resistant Sumai3 accumulated 7-fold more P450 transcripts than did the FHB-susceptible Annong8455, while 84-fold more P450 transcripts were accumulated in the FSB-resistant Annong8455 than the FSB-susceptible Sumai3. A Fusarium strain with a disrupted Tri5 gene, which is not able to produce the first enzyme essential for trichothecene mycotoxin biosynthesis, also induced more P450 transcripts in FHB- and FSB-resistant cultivars. The fungal activation of the P450 gene was more profound in the FSB-resistant reaction than the FHB-resistant reaction relative to their susceptible counterparts. DON triggered a differential expression of the P450 gene with comparable patterns in spikes and seedlings in a resistance-dependent manner. These results may provide a basis for dissecting mechanisms underlying FHB and FSB resistance reactions in wheat and revealing functions of the cytochrome P450 in plant detoxification and defense.
One of the primary goals of nuclear physics is to understand the force between nucleons, which is a necessary step for understanding the structure of nuclei and how nuclei interact with each other. ...Rutherford discovered the atomic nucleus in 1911, and the large body of knowledge about the nuclear force that has since been acquired was derived from studies made on nucleons or nuclei. Although antinuclei up to antihelium-4 have been discovered and their masses measured, little is known directly about the nuclear force between antinucleons. Here, we study antiproton pair correlations among data collected by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC), where gold ions are collided with a centre-of-mass energy of 200 gigaelectronvolts per nucleon pair. Antiprotons are abundantly produced in such collisions, thus making it feasible to study details of the antiproton-antiproton interaction. By applying a technique similar to Hanbury Brown and Twiss intensity interferometry, we show that the force between two antiprotons is attractive. In addition, we report two key parameters that characterize the corresponding strong interaction: the scattering length and the effective range of the interaction. Our measured parameters are consistent within errors with the corresponding values for proton-proton interactions. Our results provide direct information on the interaction between two antiprotons, one of the simplest systems of antinucleons, and so are fundamental to understanding the structure of more-complex antinuclei and their properties.
Petroleum hydrocarbon is one of the dangerous substances in the process of petroleum development, refining, processing, transportation, and production. In the related activities of the petroleum ...industry, the output is large, and improper treatment will cause pollution to the surrounding environment. It is an urgent problem to conduct harmless and resource treatment of petroleum hydrocarbon polluted soil. Plant enrichment, as an environmentally friendly and pollution-free technical means, has the advantages of low cost and small change to the soil environment and effectively solves the problems of excessive heavy metals in petroleum hydrocarbons through plant enrichment. In this paper, the development process of plant enrichment, remediation methods, and plant enrichment of typical heavy metals (Cd, Hg, Zn) in petroleum hydrocarbon-polluted soil were systematically introduced. Through investigation, the mechanism and influencing factors of plant enrichment of heavy metals in the presence of petroleum hydrocarbons were summarized and analyzed, and the possible development direction of plant enrichment technology in the future was prospected.
Abstract
This study was conducted to investigate the effects of dietary manganese-methionine (Mn-Met) supplementation on the egg quality of laying hens. A total of 480 Jinghong-1 strain layers aged ...53 wk were divided into 5 groups with 6 replicates of 16 layers. Birds in the control group were fed a diet supplemented with 60 mg Mn/kg in the form of MnSO4; the birds in other 4 experimental groups were fed a diet supplemented with 20, 40, 60, and 80 mg Mn/kg as Mn-Met, respectively. Dietary Mn-Met treatments significantly affected (P < 0.05) the albumen height, yolk color, and Haugh unit compared to those of the control diet. The Mn contents in the eggshell increased (P < 0.01) significantly by increasing the Mn-Met supplementation, whereas Mn content in eggshell was triple that in the yolk or albumen. Compared with the 60 mg/kg Mn-Met group, the transverse surface in the control group had (P < 0.01) a greater width of mammillary cones, and there were obvious cracks on the outer surface in the control. There was no difference (P > 0.05) in the eggshell gland (ESG) in the expression of calbindin-D28k (CaBP-D28k) mRNA in response to any diet treatment. In conclusion, dietary Mn-Met supplementation increased internal egg quality and the ultrastructure of the eggshell. Compared to the control, 60 mg/kg Mn-Met treatment resulted in improving egg quality, and 20 mg/kg Mn-Met treatment had similar effects the control treatment had on the egg quality. This indicates that the inorganic Mn can be replaced by the lower concentration of Mn-Met.
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