Colorimetric and surface-enhanced Raman scattering dual-mode lateral flow immunosensor using phage-displayed shark nanobody for the detection of crustacean allergen tropomyosin.

Tropomyosin (TM) is the primary allergenic protein responsible for crustacean food allergies, and thus sensitive and rapid methods are required for the screening of crustacean TM in food. In this study, using the phage-displayed shark nanobody (PSN) as a multifunctional biomaterial, we developed a colorimetric and surface-enhanced Raman scattering dual-mode lateral flow immunosensor (CM/SERS-LFI) for competitive detection of crustacean TM. The SERS tag AuMBA@AgNPs with the Raman signal molecule 4-mercaptobenzoic acid (4-MBA) was prepared and immobilized on the PSN to construct the immunoprobe AuMBA@Ag-PSN. The probe can identify free TM that competes with TM on the T-line, and the optimized CM/SERS-LFI enables quantitative analysis of TM using the probe with a limit of detection (LOD) of 0.0026 µg/mL (SERS mode) and 0.0057 µg/mL (colorimetric mode), respectively. Additionally, it can implement a qualitative analysis by the naked eye with a visual LOD of 0.01 µg/mL. The CM/SERS-LFI exhibited excellent performance in the tests of selectivity, accuracy, precision, and stability. Moreover, the method's effectiveness in the analysis of real samples was confirmed by a commercial ELISA kit. Therefore, the developed CM/SERS-LFI was demonstrated to be a powerful and reliable tool for the rapid and sensitive detection of crustacean TM in food.

Illuminating the path: aggregation-induced emission for food contaminants detection.

Food safety is a global concern that deeply affects human health. To ensure the profitability of the food industry and consumer safety, there is an urgent need to develop rapid, sensitive, accurate, and cost-effective detection methods for food contaminants. Recently, the Aggregation-Induced Emission (AIE) has been successfully used to detect food contaminants. AIEgens, fluorescent dyes that cause AIE, have several valuable properties including high quantum yields, photostability, and large Stokes shifts. This review provides a detailed introduction to the principles and advantages of AIE-triggered detection, followed by a focus on the past five years' applications of AIE in detecting various food contaminants including pesticides, veterinary drugs, mycotoxins, food additives, ions, pathogens, and biogenic amines. Each detection principle and component is comprehensively covered and explained. Moreover, the similarities and differences among different types of food contaminants are summarized, aiming to inspire future researchers. Finally, this review concludes with a discussion of the prospects for incorporating AIEgens more effectively into the detection of food contaminants.

Ubiquitin ligase RNF5 serves an important role in the development of human glioma.

The ubiquitin ligase ring finger protein 5 (RNF5) has previously been associated with the development of breast cancer. Patients with breast cancer and high RNF5 expression have been demonstrated to have a shorter survival time compared with patients with low RNF5 expression. However, the role of RNF5 in human glioma has not been determined. The present study analyzed the role of RNF5 in gliomas using bioinformatics analysis. The results revealed that RNF5 was differentially expressed in non-cancerous brain tissues and different grades of glioma. Furthermore, a high RNF5 expression in patients with glioma was associated with an improved prognosis compared with patients with low expression. Gene Set Enrichment Analysis revealed that RNF5 was particularly associated with 'Wnt signaling pathway', 'apoptosis', 'focal adhesion' and 'cytokine-cytokine receptor interaction' in patients with glioma. Additionally, 4 potential ubiquitination substrates for RNF5 were predicted, including sorting nexin 10, proprotein convertase subtilisin/kexin type 1, leucine rich glioma inactivated 1 and solute carrier family 39 member 12. These findings provided the basis for further investigation on the role of RNF5 in tumors.

One-Way Localized Adiabatic Passage in an Acoustic System.

Stimulated adiabatic passage utilizes radiation pulses to efficiently and selectively transfer population between quantum states, via an intermediate state that is normally decaying. In this Letter, we propose the analog of stimulated adiabatic passage in an acoustic system. It is realized with cavities that correlate through adiabatically time-varying couplings, where the cavities and time-varying couplings mimic discrete states and radiation pulses, respectively. With appropriate arrangements of coupling actions, an acoustic wave can be efficiently transferred from the initial excited cavity to the target cavity in the forward direction, immune to the intermediate dark cavity. On the other hand, for the backward propagation, the acoustic energy is perfectly localized in the intermediate dark cavity and completely dissipated. We analytically, numerically, and experimentally demonstrate such unidirectional sound localization and unveil the essential role of zero-eigenvalue eigenstates in the adiabatic passage process.

Bioinformatic analysis of Cacybp-associated proteins using human glioma databases.

The ubiquitin-proteasome system is the primary cellular pathway for protein degradation, mediating 80% of intracellular protein degradation. Because of the widespread presence of ubiquitin-modified protein substrates, ubiquitination can regulate a variety of cellular activities including cell proliferation, apoptosis, autophagy, endocytosis, DNA damage repair, and immune responses. With the continuous generation of genomics data in recent years it has become particularly important to analyze these data effectively and reasonably. Cacybp forms a complex with the E3 ubiquitinated ligase Siah1 to participate in ubiquitination. We analyzed Cacybp-associated genes using the Gene Expression Omnibus (GEO) and CGGA (Chinese Glioma Genome Atlas) databases and identified 121 differentially expressed genes (DEGs), of which 46 were downregulated and 75 were upregulated. The biological processes, molecular functions, and protein-protein interaction (PPI) network of differential genes were analyzed by Cytoscape software and STRING software. We found no difference in Cacybp expression among different grades of gliomas and there was no significant association between the expression level of Cacybp and the prognosis of patients with glioma in LGG and GBM. © 2019 IUBMB Life, 1-8, 2019.

A smart bottom-up strategy for fabrication of complex hydrogel constructs with 3D controllable geometric shapes through dynamic interfacial adhesion.

A novel and facile dynamic interfacial adhesion (DIA) strategy has been successfully applied in the reversible fabrication of complex 3D hydrogel constructs based on dynamic covalent bonds (DCBs). By tailoring the geometry of gel building blocks (GBBs) and incorporating stimuli-responsive units, various shapes could be easily achieved.

PPARα Regulates the Proliferation of Human Glioma Cells through miR-214 and E2F2.

Peroxisome proliferator-activated receptor α (PPARα) is a member of the nuclear hormone receptor superfamily and functions as a transcription factor. Previous work showed that PPARα plays multiple roles in lipid metabolism in tissues such as cardiac and skeletal muscle, liver, and adipose tissue. Recent studies have discovered additional roles for PPARα in cell proliferation and metabolism, as well as tumor progression. PPARα is aberrantly expressed in various cancers, and activated PPARα inhibits the proliferation of some tumor cells. However, there have been no studies of PPARα in human gliomas. Here, we show that PPARα is expressed at lower levels in anaplastic gliomas and glioblastoma multiforme (GBM) tissue compared with low-grade gliomas tissue, and low expression is associated with poor patient prognosis. PPARα activates transcription of dynamin-3 opposite strand (DNMO3os), which encodes a cluster of miR-214, miR-199a-3p, and miR-199a-5p microRNAs. Of these, miR-214 is transcribed at particularly high levels. PPARα-induced miR-214 expression causes downregulation of its target E2F2. Finally, miR-214 overexpression inhibits glioma cell growth in vitro and in vivo by inducing cell cycle arrest in G0/G1. Collectively, these data uncover a novel role for a PPARα-miR-214-E2F2 pathway in controlling glioma cell proliferation.

miR­218 inhibits the proliferation of human glioma cells through downregulation of Yin Yang 1.

Malignant glioma is the most common cancer type of the nervous system and the mechanisms driving the occurrence and development remain unclear, preventing effective treatment of this disease. Therefore, novel and efficient therapies for glioma are required. MicroRNAs (miRNAs) are small non­coding RNAs that act as oncogenes or tumor suppressors in human cancer. In the present study, it was confirmed that Yin Yang­1 (YY1), a transcription factor that is part of the polycomb group protein (PcG) family, is a direct target of miR­218 in human glioma cells. It was demonstrated that YY1 promoted glioma cell proliferation and miR­218 could inhibit glioma cell proliferation by targeting YY1, and indirectly reduced the degradation of p53. Together the results indicate that miR­218 functions as a tumor suppressor in human glioma and suggest that overexpression of miR­218 may be a potential strategy for the treatment of human glioma in the future.

[Over-expression of miR-497 promotes the proliferation of U87 glioma cells by targeting neuregulin receptor degradation protein 1].

Objective To investigate the effect of miR-497 over-expression on the proliferation of U87 human glioma cells. Methods We packaged both pGLV3/H1-NC lentivirus as a negative control group and pGLV3/H1-miR-497 lentivirus as an experimental group, and then constructed U87-NC and U87-miR-497 cell lines, respectively. The relationship between miR-497 and neuregulin receptor degradation protein 1 (Nrdp1) was analyzed by luciferase reporter assay in U87 cells; cell colony formation assay was used to detect cell proliferation and flow cytometry to detect cell cycle; the expressions of Nrdp1, AKT and phosphorylated AKT (p-AKT) were determined by Western blotting. Results We successfully packaged pGLV3/H1-NC and pGLV3/H1-miR-497 lentivirus, and obtained stable U87-NC and U87-miR-497 cell lines. When miR-497 was over-expressed in U87 cells, the cell colony formation ability was enhanced compared with the control group U87-NC. The luciferase reporter assay confirmed that miR-497 targeted Nrdp1 in U87 cells. In the stable infected cells, the level of Nrdp1 protein decreased and p-AKT protein increased, while the AKT protein did not change significantly after over-expression of miR-497. Conclusion Over-expression of miR-497 promotes the proliferation of glioma cells U87 by targeting Nrdp1.

Observation of low-loss broadband supermode propagation in coupled acoustic waveguide complex.

We investigate analytically, numerically, and experimentally the low-loss supermode propagation in a coupled acoustic waveguide complex within a broadband. The waveguide complex is implemented with air channels coupled via an ultrathin metafluid layer. We analytically derive the field distribution of incident sound needed for producing acoustic supermodes, and verify the periodically revival propagation in coupled waveguide systems numerically and experimentally. We find out that the supermode wavelength becomes longer for higher mode order or lower frequency. We have also demonstrated the robust propagation of supermodes in broadband. Our scheme can in principle be extended to three dimensions and the ultrasound regime with simplicity and may promote applications of high-fidelity signal transfer in complicated acoustic networks.

[The protective effect of exenatide on the renal injury in diabetic rats].

OBJECTIVE: To investigate the protective effect of exenatide (Ex) on the renal injury in streptozotocin-induced diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into 2 groups:normal control group (NC group, n=8) and model group. Model group was injected with low dose of streptozotocin (30 mg·kg-1) after the rats were fed with high fat and high glucose diet for 4 weeks. Seventy-two hours later, rats of blood glucose level ≥ 16.7 mmol·L-1 were divided into diabetes mellitus group (DM, n=10) and two exenatide-treated groups (Ex groups,3 or 6µg·kg-1, n=8). Ex groups subcutaneously injected with exenatide for 12 weeks, but NC group and DM group were injected with the same volume of solvent. Changes in glycolipid metabolism and renal function such as serum creatinine (Scr), urine creatinine (Ucr), blood urea nitrogen (BUN), 24 hour urine micro-albumin (24 h UMA)in the 4 groups of rats were determined and creatinine clearance rate (Ccr) were calculated. Renal oxidative stress parameters such as superoxide dismutase (SOD), malondialdehyde(MDA), glutathione per-oxidase (GSH-Px) were measured. Hematoxylin-eosin (HE) staining was used to examine pathological morphology in the renal tissues and ELISA was performed to determine the level of advanced glycation end products(AGEs), the glycosylation end product in renal tissues. RESULTS: Compared to the DM group,glycolipid metabolic abnormalities in the exenatide-treated groups were significantly ameliorated with lower levels of blood glucose,HbAlc, cholesterol and triglyceride (P < 0.05). The renal function index was markedly improved (P < 0.05) with Ccr reduced, indicating a high glomerular filtration status. Meanwhile, exenatide treatment improved the diabetes-induced pathological changes in renal morphology, substantially increased the activities of SOD and GSH-Px, and reduced the levels of MDA and AGEs. CONCLUSIONS: Exe-natide has the renal protective effect probably by the mechanisms of inhibition of AGEs production and reduction of oxidative stress in the renal tissues of diabetic rats.

Disruption of the EZH2/miRNA/ß-catenin signaling suppresses aerobic glycolysis in glioma.

EZH2 is up-regulated in various cancer types, implicating its role in tumorigenesis. Our recent data have shown that repression of EZH2 inhibited glioma growth by inhibition ß-catenin signaling. Here, we identified several miRNAs that were repressed by EZH2, which in turn regulate ß-catenin expression by its 3'UTR, such as miR-1224-3p, miR-328 and miR-214. Further, EZH2 silenced miR-328 expression by binding to miR-328 promoter and promoting methylation of miR-328 promoter. Finally, miR-328 largely abrogated EZH2 effects on ß-catenin expression and glucose metabolism in glioma cells. Taken together, we propose a model for a coordinated EZH2-ß-catenin oncoprotein axis, and epigenetic link between histone modification and DNA methylation, mediated by EZH2-scilenced miRNAs.

Comprehensive portrait of recurrent glioblastoma multiforme in molecular and clinical characteristics.

Glioblastoma multiforme is the most common primary malignant brain tumor in adults. In addition to poor response to treatment, a high recurrence rate contributes to the poor prognosis. The purpose of this study was to investigate the genetical and clinical characteristics of recurrent glioblastoma. We used whole transcriptome sequencing data to examine the distribution of molecular subtypes and gene signatures in 22 recurrent glioblastoma taken from the Chinese population, and further analyzed biological progression of the tumors, when compared with primary glioblastoma. The proportion of the classical subtype in recurrent ones (22%) was lower than that in primary glioblastoma (36%). The frequency of IDH1 mutations in recurrent glioblastomas was nearly twice that in primary glioblastomas. TP53 mutations were fewer in proneural recurrent glioblastomas (20%) but frequent in classical recurrent glioblastomas (80%). The most common sites of recurrent glioblastomas were the temporal lobe (41%). In patients diagnosed with recurrent glioblastoma multiforme, 64% were younger than 50 years. Gene set enrichment analysis revealed that chromatin fracture, repair, and remodeling genes were enriched in recurrent glioblastoma. Our results highlight the differences in clinical features, molecular subtypes and gene alterations between primary and recurrent glioblastoma and may be helpful for targeted therapy for recurrent glioblastoma.

NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells.

Aerobic glycolysis (production of lactate from glucose in the presence of oxygen) is a hallmark of cancer. Fenofibrate is a lipid-lowering drug and an agonist of the peroxisome proliferator-activated receptor alpha (PPARα). We found that FF inhibited glycolysis in a PPARα-dependent manner in glioblastoma cells. Fenofibrate inhibited the transcriptional activity of NF-κB/RelA and also disrupted its association with hypoxia inducible factor1 alpha (HIF1α), which is required for the binding of NF-κB/RelA to the PKM promoter and PKM2 expression. High ratios of PKM2/PKM1 promote glycolysis and inhibit oxidative phosphorylation, thus favoring aerobic glycolysis. Fenofibrate decreased the PKM2/PKM1 ratio and caused mitochondrial damage. Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM).

PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop.

Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than non-tumor cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let-7a/c-Myc/hnRNPA1/PKM2 signaling in glioma cell glucose metabolism. PKM2 depletion via siRNA inhibits cell proliferation and aerobic glycolysis in glioma cells. C-Myc promotes up-regulation of hnRNPA1 expression, hnRNPA1 binding to PKM pre-mRNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let-7a, which functionally targets c-Myc, whereas hnRNPA1 blocks the biogenesis of let-7a to counteract its ability to downregulate the c-Myc/hnRNPA1/PKM2 signaling pathway. The down-regulation of c-Myc/ hnRNPA1/PKM2 by let-7a is verified using a glioma xenograft model. These results suggest that let-7a, c-Myc and hnRNPA1 from a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of glioma cells. These findings elucidate a new pathway mediating aerobic glycolysis in gliomas and provide an attractive potential target for therapeutic intervention.

A pseudogene-signature in glioma predicts survival.

Pseudogene was recognized as a potential tumor suppressor or oncogene in varies of diseases, however its roles in glioma have not been investigated. Our study was to identify the pseudogene-signature that predicted glioma survival. Using a pseudogene-mining approach, we performed pseudogene expression profiling in 183 glioma samples from the Chinese Glioma Genome Atlas (CGGA) and set it as the training set. We found a six-pseudogene signature correlated with patients' clinical outcome via bioinformatics analyses (P ≤ 0.01), and validated it in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) containing 350 cases. A formula calculating the risk score based on the six-pseudogene signature was introduced and the patients of CGGA set were classified into high-risk group and low-risk group with remarkably different survival (P < 0.001) based on their scores. The prognostic value of the signature was confirmed in the REMBRANDT set. Though the function of these pseudogenes is not clear, the identification of the prognostic pseudogenes indicated the potential roles of pseudogenes in glioma pathogenesis and they may have clinical implications in treating glioma.

Surfactant-free synthesis of Fe3O4@PANI and Fe3O4@PPy microspheres as adsorbents for isolation of PCR-ready DNA.

Magnetic separation with composite microspheres presents an alternative strategy for applications in biomedical and bioengineering fields. However, the synthesis of core-shell structured magnetic composites universally assumes the surfactant-directing and/or silica-assisting polymerization approach to modify and stabilize the magnetic cores. In this paper, we report on the surfactant-free synthesis of well-defined core-shell structured Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres with high magnetization. The temperature dependence of magnetization of the samples was examined as a function of temperature between 3 and 300 K in an applied field of 500 Oe. It was found that the blocking temperature (T(B)) values of the composite spheres are well above the room temperature. The small variation in magnetization as the temperature changes renders the composite spheres a suitable candidate when used at elevated temperatures. Also, the genomic DNA can be effectively isolated from Aspergillus niger (A. niger) cells with the composite microspheres, using a PEG-NaCl binding buffer and a phosphate eluting buffer. The magnetic isolation of genomic DNA with the composite microspheres was shown to be superior to the conventional phenol-chloroform extraction, which was confirmed by agarose gel eletrophoresis and polymerase chain reaction (PCR) diagnosis. The Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres presented here have great potential in enzyme immobilization, drug delivery, catalysis, and sensors.