The molecular mechanism by which roquin controls the expression of inducible costimulator (ICOS) to prevent autoimmunity remains unsolved. Here we show that in helper T cells, roquin localized to ...processing (P) bodies and downregulated ICOS expression. The repression was dependent on the RNA helicase Rck, and roquin interacted with Rck and the enhancer of decapping Edc4, which act together in mRNA decapping. Sequences in roquin that confer P-body localization were essential for roquin-mediated ICOS repression. However, this process did not require microRNAs or the RNA-induced silencing complex (RISC). Instead, roquin bound ICOS mRNA directly, showing an intrinsic preference for a previously unrecognized sequence in the 3' untranslated region (3' UTR). Our results support a model in which roquin controls ICOS expression through binding to the 3' UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The molecular mechanism by which Roquin controls ICOS expression to prevent autoimmunity remains unsolved. Here we show that in helper T cells Roquin localized to processing bodies and downregulated ...ICOS expression. The repression was dependent on Rck, and Roquin interacted with Rck and Edc4, which cooperate in mRNA decapping. Sequences in Roquin that confer P body localization were essential for Roquin-mediated ICOS repression. This process did not require microRNAs or the RISC. Instead, Roquin bound ICOS mRNA directly, exhibiting an intrinsic preference for a previously unrecognized sequence in the 3' untranslated region. Our results support a model in which Roquin controls ICOS expression through binding to the 3'UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, ...which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation.
Chronic liver disease is rising in western countries and liver cirrhosis is the 12th leading cause of death worldwide. Simultaneously, use of gastric acid suppressive medications is increasing. Here, ...we show that proton pump inhibitors promote progression of alcoholic liver disease, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis in mice by increasing numbers of intestinal Enterococcus spp. Translocating enterococci lead to hepatic inflammation and hepatocyte death. Expansion of intestinal Enterococcus faecalis is sufficient to exacerbate ethanol-induced liver disease in mice. Proton pump inhibitor use increases the risk of developing alcoholic liver disease among alcohol-dependent patients. Reduction of gastric acid secretion therefore appears to promote overgrowth of intestinal Enterococcus, which promotes liver disease, based on data from mouse models and humans. Recent increases in the use of gastric acid-suppressive medications might contribute to the increasing incidence of chronic liver disease.Proton pump inhibitors (PPIs) reduce gastric acid secretion and modulate gut microbiota composition. Here Llorente et al. show that PPIs induce bacterial overgrowth of enterococci, which, in turn, exacerbate ethanol-induced liver disease both in mice and humans.
In this paper, a core-shell based on the Fe3O4@SiO2@Au nanoparticle amplification technique for a surface plasmon resonance (SPR) sensor is proposed. Fe3O4@SiO2@AuNPs were used not only to amplify ...SPR signals, but also to rapidly separate and enrich T-2 toxin via an external magnetic field. We detected T-2 toxin using the direct competition method in order to evaluate the amplification effect of Fe3O4@SiO2@AuNPs. A T-2 toxin–protein conjugate (T2-OVA) immobilized on the surface of 3-mercaptopropionic acid-modified sensing film competed with T-2 toxin to combine with the T-2 toxin antibody–Fe3O4@SiO2@AuNPs conjugates (mAb-Fe3O4@SiO2@AuNPs) as signal amplification elements. With the decrease in T-2 toxin concentration, the SPR signal gradually increased. In other words, the SPR response was inversely proportional to T-2 toxin. The results showed that there was a good linear relationship in the range of 1 ng/mL~100 ng/mL, and the limit of detection was 0.57 ng/mL. This work also provides a new possibility to improve the sensitivity of SPR biosensors in the detection of small molecules and in disease diagnosis.
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•A millimeter-sized nanocomposite (Ti-NS) was fabricated by encapsulating Ti(IV) oxides in polymer.•Ti-NS exhibits highly efficient phosphate sequestration in aqueous ...solutions.•Adsorption mechanism was investigated and discussed.•Ti-NS could be effectively regenerated for repeated use.
Removal of phosphate from industrial is important to prevent the occurrence of eutrophication and adsorption may serve as a powerful supplement to chemical or biological phosphate sequestration. Here, a novel nanocomposite material Ti-NS is proposed to enhance phosphate removal from aqueous system by impregnating titanium oxides inside a millimeter-sized polymer (NS). The resulting Ti-NS possesses two distinct sites for phosphate removal, the ammonium groups bound to the NS matrix and the loaded titanium oxide nanoparticles. The maximum adsorption capacity of Ti-NS occurs at near-neutral pH, and exhibited fast kinetic behavior for phosphate uptake which could be well described by the pseudo-first-order model and intraparticle diffusion model. Compared with NS host, Ti-NS exhibits much higher capacity and preference toward phosphate removal in the presence of competing anions at greater levels. SEM-EDS and XPS study confirmed that phosphate uptake by Ti-NS was involved in two distinct adsorption interactions, i.e. ion exchange to the quaternary ammonium groups of host and ligand exchange reactions to the hydroxyl groups of titanium oxides. Cyclic adsorption and regeneration runs in fixed-bed indicated that Ti-NS is of great potential for phosphate removal from the water containing competitive anions at higher levels. Moreover, the exhausted nanocomposite can be effectively regenerated by NaOH-NaCl solution for recycle use with negligible capacity loss. All the results demonstrated that prepared Ti-NS was a promising alternative adsorbent for efficient phosphate removal from contaminated water.
Neonicotinoid-based pesticides are extensively used owing to their broad insecticidal spectrum and activity. We developed neonicotinoid dinotefuran (DIN)-loaded chitosan-gelatin microspheres using a ...spray-drying technology, resulting in a pH- and temperature-responsive controlled-release system. Upon introducing chitosan into the triple-helix structure of gelatin, the physically modified gelatin microspheres became smooth, round, and solid, improving their thermal storage stability. The spray-drying parameters were optimized using three-dimensional surface plots. When scaled up under optimal conditions, the corresponding loading content and encapsulation efficiency were 21.5% and 98.17%, respectively. Compared with commercial dinotefuran granules, our biodegradable composite carriers achieved the immobilization of dinotefuran to reduce pesticide leaching by 5.57–19.89% in soil, improved the soil half-life of DIN, and improved its cumulative absorption by plants. Therefore, the microspheres showed better efficacy against Trialeurodes vaporariorum. Our results confirm that this simple approach can improve the utilization efficiency of neonicotinoids, decrease leaching loss, and promote ecological safety.
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•The physically modified microspheres became round, solid, and stable.•A pH- and temperature-sensitive, controlled-release microsphere system was developed.•Dinotefuran-loaded gelatin-chitosan microspheres reduced the pesticide leaching.•The soil half-life of dinotefuran was increased by 11 days with its accumulation in leaves.•The microspheres showed a better efficacy against Trialeurodes vaporariorum.
In the area of catalysis, selective reduction of nitro compounds to amino compounds is a colossal challenge due to the existence of competitive reducible functional groups. Herein, an Fe-based ...catalyst FeSAs/Fe2O3ACs/N-doped polyhedral carbon (NPC) has been designed and synthesized. As we expected, compared with FeSAs and FeNPs, FeSAs/Fe2O3ACs/NPC shows excellent catalytic performance (turnover frequency up to 1923 h–1, calculated with nitrobenzene), chemoselectivity, and tolerance during the hydrogenation reaction of nitro compounds under room temperature because of the synergistic effects between FeSAs and Fe2O3ACs. The theoretical calculations show that FeSAs prefers to undergo hydrazine decomposition to generate hydrogen and the Fe2O3ACs surface is more active toward the nitrobenzene reduction to aniline.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing ...a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio OR, 12.915; 95% confidence interval CI, 3.342–49.916; P < 0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272–2.813; P = 0.002). The model’s area under the curve (AUC) was 0.882 (95% CI: 0.808–0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809–0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775–0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.
Cardiovascular malady (CVM) isn't just the essential driver of death in created western nations, yet additionally, its sickness load is expanding in China. Oxidative pressure initiated free radicals ...assume a basic job in cell forms involved in atherosclerosis and numerous other heart illnesses. Quercetin (QC) is cancer prevention agents medicate which is demonstrated that successfully secures against CVMs. Encapsulations of medications in polymeric materials are generally utilized in creating continued and controllable medication discharge, or to keep away from the debasement of non-discharged medications. In this present work, a novel arrangement of polymeric superparamagnetic nano-silica (SiN)@poly(lactic-co-glycolic acid) (PLGA) (SiN@PLGA) stacked with QC was created by means of lyophilization method so as to improve poor watery solvency and steadiness of the medication with the point of preventing atherosclerosis. The aftereffects of SEM investigation and the checking, TEM affirmed the manufacture of the circular nanocomposite, smooth surface, and thin size dispersion. The discharge profile of QC from the particles was explored by deciding the medication sum discharged at explicit interims for by iridescence. The data got from this investigation encourages the structure and manufacture of nanocomposite as conceivable conveyance frameworks for epitome, assurance and controlled arrival of the flavonoid QC which is expecting to secure against CVMs.
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•SiN@PLGA-polymeric biocomposite of quercetin were developed.•SiN@QC-PLGA nanocarrier showed significant drug release.•SiN@QC-PLGA nanocarrier showed significant in vitro cardiac proteins expression activity.•SiN@QC-PLGA nanocarrier show negligible toxicity to the mice.
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