Background
MicroRNAs (miRNAs) have become increasingly prevalent as a result of the association of their deregulation with neurodegenerative disorders, especially Alzheimer's disease (AD). However, ...the association between miRNAs and AD remains unclear.
Methods
In the present study, Nine representative miRNA datasets were selected for the identification of the critical miRNAs by analyzing the overlapping relationships among them. TargetScan software (http://www.targetscan.org) was used to predict the target genes of these miRNAs. In addition, the Database for Annotation Visualization and Integrated Discovery (DAVID; http://david.abcc.ncifcrf.gov) and TfactS (http://www.tfacts.org) datasets were used for combined analysis of functional enrichment and transcription factor (TF) analysis.
Results
Thirteen key miRNAs were identified, of which four were significantly up‐regulated (hsa‐miR‐101,hsa‐miR‐155, has‐miR‐34a, has‐miR‐9) and eight were found to be significantly down‐regulated (hsa‐let‐7d‐5p, hsa‐let‐7 g‐5p, hsa‐miR‐15b, has‐miR‐191‐5p, hsa‐miR‐125b, has‐miR‐26b‐5p, hsa‐miR‐29b, hsa‐miR‐342‐3p). The functional enrichment analysis indicated that up‐regulated signature miRNA targets were associated with transcription from the RNA polymerase II promoter process and the chemical synaptic transmission process. Down‐regulated signature miRNA targets were mostly enriched with respect to positive regulation of transcription from the RNA polymerase II promoter process, p53 signaling, and microRNAs in cancer pathways. TF analysis showed that 87 TFs were influenced by the up‐regulated miRNAs, and 134 TFs were influenced by the down‐regulated miRNAs. In total, 70 (45.5%) TFs were affected by both up‐regulated and down‐regulated miRNAs.
Conclusions
In summary, 13 key miRNAs were found to have a vital function in the pathological progress of AD, as well as the target genes and TFs of these miRNAs. The potential functions of these miRNAs as diagnostic and therapeutic targets of the AD are revealed by the present study.
The simplicity of the green-synthesized routine and the availability of surface modification of diverse bioactive molecules make noble metal nanostructures highly suitable as multifunctional ...biomaterials for biological and biomedical application. Here, we report the preparation of trypsin stabilized gold nanoclusters (try-AuNCs) with near-infrared fluorescence for biosensing heparin based on surface plasmon enhanced energy transfer (SPEET) and folic acid (FA) modified try-AuNCs for in vivo cancer bioimaging. The SPEET/try-AuNCs fluorescence biosensor was designed via heparin mediated energy transfer between try-AuNCs and cysteamine modified gold nanoparticles (cyst-AuNPs). The developed SPEET/try-AuNCs fluorescence biosensor allowed sensitive and selective detection of heparin with a linear range of 0.1–4.0 μg mL–1 and a detection limit (3s) of 0.05 μg mL–1. The relative standard deviation for eleven replicate detections of 2.5 μg mL–1 heparin was 1.1%, and the recoveries of the spiked heparin in human serum samples ranged from 97% to 100%. In addition, folic acid was immobilized on the surface of try-AuNCs to ameliorate the specific affinity of AuNCs for tumors, and the near-infrared fluorescent FA-try-AuNCs were applied for in vivo cancer imaging of high folate receptor (FR) expressing Hela tumor. In vivo study of the dynamic behavior and targeting ability of FA-try-AuNCs probe to Hela tumor bearing mice and normal nude mice validated the high specific affinity of FA-try-AuNCs probe to FR positive tumors. The results show that the prepared try-AuNCs have great potential as multifunctional biomaterials for biosensing biomolecules with SPEET mode and in vivo cancer imaging with high targeting ability.
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•A universal sensing platform for both analyzing and removing heavy metal was proposed.•Simple amino-group functionalization would light the MOF materials.•Amino-functionalized MOF ...showed great adsorption ability for Fe3+, Cu2+ and Pb2+.•Possible mechanisms of detection and adsorption were fully investigated.•The study opens up new potential of MOF application via proper surface modification.
Pollution generated by heavy metals has become a global environmental issue with much public concern. For the first time, the current research presented series of amino-decorated MOFs as a universal sensing platform that demonstrated great potential for detecting and removing heavy metals with remarkable specificity and capability. Concretely, the amino-functionalized MIL-101(Fe) synthesized via a simple one-step method possessed satisfactory fluorescence due to the linker emission, and the excellent sensing performance of MIL-101-NH2 in detecting Fe3+, Cu2+ and Pb2+ with a low LOD and a broad liner range could be achieved. Furthermore, MIL-101-NH2 exhibited great adsorption ability and reusability in removing Fe3+, Cu2+ and Pb2+ from aqueous solution, and the saturated adsorption capacities reached up to 3.5, 0.9 and 1.1 mM/g. More importantly, other series MOFs constructed from organic linkers with amino groups decoration including MIL-101-NH2(Cr), MIL-53-NH2(Al), UiO-66-NH2(Zr) and MOF-5-NH2(Zn) also showed similar performance in the detection and removal of metal ions. Possible mechanisms for the fluorescence quenching and adsorption were investigated. All in all, the research results not only met the requirements of sensitively detecting and efficiently removing heavy metals, but also provided novel inspirations for future application of MOFs in the field related to environmental protection via specific surface functionalization.
Pancreatic ductal adenocarcinoma (PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs (circRNAs) may be functional and bind to microRNAs and consequently, ...influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated.
miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman's correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA (siRNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting.
ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues (P = 0.002). However, miR-7 expression showed the opposite trend (P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC (rs = −0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion (3.72 ± 2.93 vs. 2.14 ± 1.26; P = 0.028) and lymph node metastasis (4.19 ± 2.75 vs. 2.32 ± 1.90; P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells (P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3).
Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway.
Nowadays, the visible-light-driven photocatalysis via advanced photocatalyst for PS activation have promising applications in wastewater treatment. Herein, for the first time, two novel MOFs@COFs ...hybrid materials (denoted as MIL-101-NH2@TpMA and UiO-66-NH2@TpMA) with nitrogen-rich building blocks were fabricated via a feasible step-by-step assembly method, and then employed as efficient photocatalytic platform coupling with sulfate radical-based advanced oxidation processes for the degradation of BPA under visible light irradiation. Detailed analyses revealed that the hybridization of MOFs and COFs could greatly boost visible light absorption, while the heterojunction formed at the interface could effectively facilitate the separation and transfer of photogenerated electron-hole pairs. More importantly, the developed solar/MOFs@COFs/PS system exhibited the excellent degradation ability toward BPA, and an incredible degradation efficiency of 99% was eventually achieved. Possible mechanism for photocatalytic degradation of BPA was also proposed. Furthermore, the prepared composites with great reusability and stability possessed a broad potential for highly effective degradation of various organic contaminants. In short, this work not only demonstrated the combination of MOFs and COFs with C3N4 active unit was a feasible strategy for improving photocatalytic activities in the degradation of organic contaminants, but also provided some novel inspirations for constructing high-efficient photocatalysts with heterostructure.
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•Two novel MOFs@COFs hybrid materials with C3N4 active units were first synthesized.•Developed solar/MOFs@COFs/PS system exhibited great degradation ability toward BPA.•Possible mechanisms for photocatalytic degradation of BPA was proposed.•As-obtained composites possessed excellent reusability and stability.•Prepared photocatalyst had a broad potential for degradation of various contaminants.
Multiple-port dc-dc converters are characterized by a variety of kinds and a large number of circuit topologies. In this article, we aim to reveal the intrinsic relationship among the topologies of ...multiple-port dc-dc converters and propose the topology derivation method. First, the voltage- and current-type ports are summarized from basic dc-dc converters, and the approach of converting current-type ports into voltage-type ports is discussed. Then, according to Kirchhoff's law, four types of multiple-input multiple-output converters named input-port-series output-port-series, input-port-series output-port-parallel, input-port-parallel output-port-series, and input-port-parallel output-port-parallel are presented. Second, the topology derivation method of multiple-port bidirectional dc-dc converters based on the voltage-type ports is studied in terms of power flow paths in various operation modes, and then the topology optimization method is proposed. Particularly, a flow diagram for the optimal design procedure is given to guide the topology derivation for some specific requirements. Based on the proposed approach, a family of multiple-port dc-dc converters can be derived, which provides lots of viable candidates for practical engineering. Furthermore, one derived converter named the parallel-type three-port bidirectional buck converter is analyzed in three operation modes to demonstrate the topology derivation. Finally, the effectiveness of the above theoretical analysis is verified by those experimental results.
•Nanobody-based dual-mode immunoassay for Ara h 3 was developed with LOD of 6.61 ng/mL.•The dominance of nanobody and B/N-CDs improved the accuracy of Ara h 3 immunoassay.•The method achieved the ...assessment of Ara h 3 in peanut contamination foodstuffs.
To improve the performance of peanut allergen Ara h 3 detection, depending on boron and nitrogen carbon dots (B/N-CDs), a nanobody (Nb) mediated dual-mode immunoassay was established, which combines the dominance of colorimetry with ratiometric fluorescence techniques. With the catalysis of Horseradish peroxidase (HRP), the oxidization of o-phenylenediamine (o-PD) in the presence of H2O2, leading to the production of yellow 2,3-diaminophenolazine (DAP) with an absorption peak at 431 nm. Owing to inner filter effect (IFE), DAP quenched the fluorescence of B/N-CDs at 426 nm, and it emerged a new emission peak at 549 nm. The fluorescence intensity ratio and absorption intensity can be utilized for quantitative analysis of Ara h 3 concentration. Under optimal conditions, the detection limits were 6.61 and 9.79 ng·mL−1, respectively. The dual-mode immunoassay was assessed containing specificity, stability, reproducibility, and practicability. This method paved the way for sensitive detection of Ara h 3 without background Interference.
The high speed of contaminants growth needs the burgeoning of new analytical techniques to keep up with the continuous demand for monitoring and legislation on food safety and environmental pollution ...control. Metal-organic frameworks (MOFs) are a kind of advanced crystal porous materials with controllable apertures, which are self-assembled by organic ligands and inorganic metal nodes. They have the merits of large specific surface areas, high porosity and the diversity of structures and functions. Latterly, the utilization of metal-organic frameworks has attracted much attention in environmental protection and the food industry. MOFs have exhibited great value as sensing materials for many targets. Among many sensing methods, fluorometric sensing is one of the widely studied methods in the detection of harmful substances in food and environmental samples. Fluorometric detection based on MOFs and its functional materials is currently one of the most key research subjects in the food and environmental fields. It has gradually become a hot research direction to construct the highly sensitive rapid sensors to detect harmful substances in the food matrix based on metal-organic frameworks. In this paper, we introduced the synthesis and detection application characteristics (absorption, fluorescence, etc.) of metal-organic frameworks. We summarized their applications in the MOFs-based fluorometric detection of harmful substances in food and water over the past few years. The harmful substances mainly include heavy metals, organic pollutants and other small molecules, etc. On this basis, the future development and possible application of the MOFs have prospected in this review paper.
As a kind of polymer material additive, phthalic acid esters (PAEs) are widely used in food industry. However, PAEs are environmental endocrine disruptors with reproductive toxicity and teratogenic ...carcinogenicity, which are difficult to be degraded in the natural environment. In this paper, gas chromatography‐mass spectrometer (GC‐MS) methods for PAEs in polyethylene wrap film were optimized. For diisobutyl phthalate (DIBP) and dibutyl phthalate (DBP) that were mainly detected, the method had a good linearity in 1 to 500 ng/g. Then, we confirmed that the migration of DIBP and DBP from polyethylene wrap film increased with time and temperature. It is found that the migration law in different food simulations well followed the migration dynamics first‐level model. The rate constant K1 and initial release rate V0 are inversely proportional to the polarity of the simulated liquid. We hope that this study can serve as a valuable reference for further research on the migration of food packing materials.
Practical Application
In this paper, we present a simple example of applying migration model to evaluate the migration behaviors of PAEs in food packaging materials along with their hazardous properties. It can serve as a valuable reference for further research on the migration of food packing materials.
It is of great significance to eliminate excessive reactive oxygen species (ROS) for treating inflammatory bowel disease (IBD). Herein, for the first time, a novel nanozyme NiCo2O4@PVP is constructed ...via a step‐by‐step strategy. Noticeably, the existence of oxygen vacancy in the NiCo2O4@PVP is helpful for capturing oxygenated compounds, while both redox couples of Co3+/Co2+ and Ni3+/Ni2+ will offer richer catalytic sites. As expected, the obtained NiCo2O4@PVP exhibits pH‐dependent multiple mimic enzymatic activities. Benefiting from the introduction of polyvinylpyrrolidone (PVP), the NiCo2O4@PVP possesses good physiological stability and excellent biosafety in stomach and intestines’ environment. Meanwhile, the NiCo2O4@PVP also presents strong scavenging activities to ROS in vitro, including •O2−, H2O2, as well as •OH. Furthermore, a dextran sodium sulfate (DSS)‐induced colitis model is established for evaluating the anti‐inflammatory activity of NiCo2O4@PVP in vivo. Based on the size‐mediated and charge‐mediated mechanisms, the nanozyme can pass through the digestive tract and target the inflamed site for oral‐administrated anti‐inflammatory therapy. More interestingly, compared with the model group, the expression levels of inflammatory factors (e.g., Interleukin‐ 6 (IL‐6), Interleukin‐ 1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and inducible nitric oxide synthase (iNOS)) in colon of mice show a significant decrease after nanozyme intervention, thereby inhibiting the development of IBD. In short, current work provides an alternative therapy for patients suffering from IBD.
The nanozyme NiCo2O4@PVP is prepared via a simple step‐by‐step strategy. NiCo2O4@PVP with multiple mimic enzymatic activities can be used as a reactive oxygen species (ROS) scavenger and is very stable in digestive tract. Moreover, the alleviating effect of NiCo2O4@PVP on the mice with colitis is also significant, exhibiting efficient inhibition for the development of colitis.
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