In recent years, antimicrobial resistance (AMR) has become one of the greatest threats to human health. There is an urgent need to develop new antibacterial agents to effectively treat AMR infection. ...Herein, a novel nanozyme platform (Cu,N-GQDs@Ru-NO) is prepared, where Cu,N-doped graphene quantum dots (Cu,N-GQDs) are covalently functionalized with a nitric oxide (NO) donor, ruthenium nitrosyl (Ru-NO). Under 808 nm near-infrared (NIR) light irradiation, Cu,N-GQDs@Ru-NO demonstrates nicotinamide adenine dinucleotide (NADH) dehydrogenase-like activity for photo-oxidizing NADH to NAD
, thus disrupting the redox balance in bacterial cells and resulting in bacterial death; meanwhile, the onsite NIR light-delivered NO effectively eradicates the methicillin-resistant Staphylococcus aureus (MRSA) bacterial and biofilms, and promotes wound healing; furthermore, the nanozyme shows excellent photothermal effect that enhances the antibacterial efficacy as well. With the combination of NADH dehydrogenase activity, photothermal therapy, and NO gas therapy, the Cu,N-GQDs@Ru-NO nanozyme displays both in vitro and in vivo excellent efficacy for MRSA infection and biofilm eradication, which provides a new therapeutic modality for effectively treating MRSA inflammatory wounds.
Abstract
Background
HuR/ELAVL1 (embryonic lethal abnormal vision 1) was a downstream target of miR-29b in some cancer cells. HuR protein exerts important prognostic effects of involving in the ...pathogenesis and development of acute myeloid leukemia (AML). This study aims to investigate the role of miR-29b-3p in biological behaviors of AML cells by targeting HuR and the involvement of the NF-κB and JAK/STAT signaling pathways.
Methods
The expressions of HuR and miR-29b-3p in AML cells were determined using RT-qPCR and Western blot, and the association between them was analyzed using the Spearman method. Next, the target relationship between HuR and miR-29b-3p was predicted by biological information databases and verified by the dual-luciferase reporter gene assay. MTS, methyl cellulose, flow cytometry and transwell assay were employed to detect the cell proliferation, clone formation, cell cycle and apoptosis, invasion and migration respectively, the effect of miR-29b-3p targeted HuR on the biological behaviors of AML cells was explored after over- /down-expression of miR-29b-3p and rescue experiment. Then, immunofluorescence assay and western blot were employed to detect location expression and phosphorylation levels of NF-κB and JAK/STAT signaling pathways related molecules respectively.
Results
HuR was negatively correlated with miR-29b-3p, and was the downstream target of miR-29b-3p in AML cells. When miR-29b-3p was overexpressed in AML cells, HuR was down-regulated, accompanied by cell viability decreased, cell cycle arrest, apoptosis increased, invasion and migration weakened. Moreover, the opposite result appeared after miR-29b-3p was down-regulated. The rescue experiment showed that miR-29b-3p inhibitor could reverse the biological effect of HuR down-regulation in AML cells. Molecular pathway results showed that miR-29b-3p could inhibit p65 expression in nucleus and phosphorylation levels of p65, IκBα, STAT1, STAT3 and STAT5.
Conclusion
miR-29b-3p can inhibit malignant biological behaviors of AML cells via the inactivation of the NF-κB and JAK/STAT signaling pathways by targeting HuR. miR-29b-3p and its target HuR can be used as a new potential molecular for AML treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The first asymmetric synthesis of a scillascillin-type homoisoflavonoid was reported. Key reactions for the asymmetric synthesis of benzocyclobutene include catalytic reductive desymmetrization of ...malonic ester and an intramolecular C–H activation of the methyl group.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that can cause gastrointestinal ulcers by affecting dopamine levels. Therefore, MPTP has been considered a toxic substance that ...causes gastric ulcer disease in experimental animals. In this study, tree shrews were used as the animal model of gastric mucosa injury, and MPTP was intraperitoneally injected at a lower MPTP dosage 2 mg/kg/day for 13 weeks, while tree shrews were not injected as the control group. Under the light microscope, local congestion or diffuse bleeding points of gastric mucosa and multiple redness and swelling bleeding symptoms on the inner wall were observed in the treatment group, as well as immune cell infiltration was found in HE staining, but no such phenomenon was observed in the control group. In order to explore the molecular basis of changes in MPTP induced gastric mucosa injury, the transcriptome and proteome data of gastric mucosa were analyzed. We observed significant differences in mRNA and protein expression levels under the influence of MPTP. The changes in mRNA and proteins are related to increased immune infiltration, cellular processes and angiogenesis. More differentially expressed genes play a role in immune function, especially the candidate genes RPL4 and ANXA1 with significant signal and core role. There are also differentially expressed genes that play a role in mucosal injury and shedding, especially candidate genes GAST and DDC with certain signaling and corresponding functions. Understanding the factors and molecular basis that affect the expression of related genes is crucial for coping with Emotionality gastric mucosa injury disease and developing new treatment methods to establish the ability to resist disease.
To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association.
We ...evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (
= 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota.
Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both
< 0.05) during follow-up and significantly associated with microbiota β-diversity (
= 0.002). α-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (
< 0.05). Seven genera (
,
,
,
,
,
, and
) were enriched in quartile 1 of GLA and in participants without type 2 diabetes.
Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.
Vascular plant one-zinc-finger (VOZ) transcription factor, a plant specific one-zinc-finger-type transcriptional activator, is involved in regulating numerous biological processes such as floral ...induction and development, defense against pathogens, and response to multiple types of abiotic stress. Six VOZ transcription factor-encoding genes (
) have been reported to exist in the soybean (
) genome. In spite of this, little information is currently available regarding
In this study,
were cloned and characterized.
genes encode proteins possessing transcriptional activation activity in yeast cells.
,
, and
gene products were widely dispersed in the cytosol, while GmVOZ1G was primarily located in the nucleus.
displayed a differential expression profile under dehydration, salt, and salicylic acid (SA) stress conditions. Among them,
showed a significantly induced expression in response to all stress treatments. Overexpression of
in soybean hairy roots resulted in a greater tolerance to drought and salt stress. In contrast, RNA interference (RNAi) soybean hairy roots suppressing
were more sensitive to both of these stresses. Under drought treatment, soybean composite plants with an overexpression of hairy roots had higher relative water content (RWC). In response to drought and salt stress, lower malondialdehyde (MDA) accumulation and higher peroxidase (POD) and superoxide dismutase (SOD) activities were observed in soybean composite seedlings with an overexpression of hairy roots. The opposite results for each physiological parameter were obtained in RNAi lines. In conclusion,
positively regulates drought and salt stress tolerance in soybean hairy roots. Our results will be valuable for the functional characterization of soybean VOZ transcription factors under abiotic stress.
In this paper, we presented an ultra-wideband multiple-input multiple-output (MIMO) antenna system with high element-isolation for the application in 5G metal-frame smartphones. We proposed T-shaped ...and C-shaped slots on the metal frame generating four resonances to enhance the bandwidth. What's more, we introduce modified H-shaped slots between each antenna-element to improve the element-isolation of MIMO antenna system. As a result, the MIMO antenna system has a wide bandwidth of 58% ranging from 3.3 to 6 GHz and the element-isolation is over 18 dB crossing the effective frequency band. Thanks to the decent element-isolation, the envelope correlation coefficient (ECC) between each antenna-element is below 0.05 providing a reliable anti-interference for the MIMO antenna system. In addition, the measured radiation efficiencies of the MIMO antenna system are higher than 40%. At last, we analyze the effects caused by user's hands and head to guarantee the robustness of the MIMO antenna system in practical applications.
Potassium oxonate, a selectively competitive uricase inhibitor, produced hyperuricemia (HUA) in rodents in a previous study. In this study, we employed the tree shrew as an animal model to study ...potassium oxonate-induced HUA. The effect of allopurinol (ALLO), a uric acid reducer, was also examined in this model. Potassium oxonate at doses of 5, 20, 40, 60, 80, 100, and 1,000 mg/kg was given intraperitoneally to tree shrews. The results showed that potassium oxonate can effectively increase the levels of uric acid in tree shrews at doses ranging from 40 to 100 mg/kg. Semiquantitative RT-PCR showed that the xanthine dehydrogenase/oxidase (XDH/XO) mRNA expression level was significantly higher in the liver tissue of tree shrews with high levels of uric acid. There were no changes in serum urea nitrogen, or serum creatinine values. ALLO can significantly decrease serum uric acid levels (P<0.01) and raise XDH/XO mRNA expression levels in the liver tissue of tree shrews with HUA. XDH/XO mRNA expression levels did not change in untreated tree shrews. Studies on acute toxicity in the tree shrew did not show any significantly abnormal signs. There were no adverse effects at the macroscopic level up to doses ≤100 mg/kg. Potassium oxonate induced acute HUA in tree shrews at lower doses compared with other animal models. Potassium oxonate-treated tree shrews may be a potential animal model for studying pathogenic mechanism and evaluating a new therapeutic agent for treatment of HUA in humans.
aquatic product, known as one of the good resources for white meat, has been widely accepted by the consumers due to its high protein, low fat, especially low cholesterol. With the fast development ...of living standards around the world, the consumer demands for high quality, nutrition, safety and freshness of ifshery food are increasing. Thus, high efifcient preservation technologies for aquatic products become particularly important. Superchilling is one of the controlled-temperature preservation technologies for seafood. Aquatic products can be kept in better quality under superchilling conditions. This review introduced the principle and development of superchilling process, mainly focusing on research progresses and technical dififculties of superchilling. The growth mechanism of ice crystals and the feasibility of application of computational lfuid dynamics in analyzing the temperatures variation and ice crystals during superchilling progress were also discussed, which will provide theoretical foundation for its improvement and application.
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