Circ_0000253 promotes the progression of osteosarcoma via the miR-1236-3p/SP1 axis.

OBJECTIVE: Circular RNAs (circRNAs) play important roles in modulating tumour progression. This study investigated the role of circ_0000253 in osteosarcoma (OS). METHODS: We downloaded the chip dataset GSE140256 from the Gene Expression Omnibus database and the circRNAs differentially expressed in OS tissue and normal tissue samples were analysed. Quantitative real-time PCR (qRT-PCR) was carried out to examine circ_0000253 expression in OS tissues and cells. Cell counting kit-8, BrdU and flow cytometry assays were performed to verify the effects of circ_0000253 on OS cell growth and apoptosis. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of miR-1236-3p with circ_0000253 and Sp1 transcription factor (SP1) mRNA 3'UTR. The effects of miR-1236-3p and circ_0000253 on SP1 expression in OS cells were detected through Western blot. KEY FINDINGS: Circ_0000253 was upregulated in OS tissues and cell lines. Circ_0000253 overexpression facilitated OS cell growth and suppressed apoptosis, whereas knocking down circ_0000253 inhibited OS cell growth and facilitated apoptosis. Circ_0000253 targeted miR-1236-3p directly and negatively modulated its expression. SP1 was miR-1236-3p's target gene and positively regulated by circ_0000253. CONCLUSION: Circ_0000253 promotes OS cell proliferation and suppresses cell apoptosis via regulating the miR-1236-3p/SP1 molecular axis.

Electrochemical synthesis of Co/Ni bimetal-organic frameworks: A high-performance SERS platform for detection of tetracycline.

Surface-enhanced Raman scattering (SERS) enables food contaminants monitoring become facile and efficient. Herein, a facile strategy of integrating three-dimensional Ni form with Co/Ni bimetal-organic frameworks combining Ag nanoparticles via electrochemical synthesis method was proposed to develop a high-performance SERS substrate (CoNi-ZIFs@Ag@NF) for efficient detection of tetracycline. The flexible Ni foam (NF) acted as scaffold which can contribute to dramatically enhancing intrinsic electrical conductivity and endowing prepared substrate with high stability and uniform distribution of Ag nanoparticles. Furthermore, the pre-concentration effect of CoNi-ZIFs@Ag@NF for target molecules enhanced SERS performance dramatically. Besides, tetracycline was sensitively detected using CoNi-ZIFs@Ag@NF with low limit of detection (1.0 × 10-11 M) and wide linear detection range (10-10 - 10-5 M) in aqueous solution. Also, the satisfactory recovery (94.45 - 114.25 %) was realized with less than 6.78 % of RSD in real samples. This method would provide a potential and high-performance substrate for SERS monitoring of tetracycline in food and environment.

Daphnoretin relieves IL-1ß-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome.

BACKGROUND: Osteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA. METHODS: The OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1ß (10 ng/mL) in vitro. Chondrocyte viability and apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative real-time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin-eosin (H&E) staining and safranin O-fast green staining. RESULTS: Daphnoretin effectively choked IL-1ß-induced chondrocyte apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1ß-induced chondrocytes. What's more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS. CONCLUSION: Daphnoretin alleviated IL-1ß-induced chondrocyte apoptosis by hindering ERS and NLRP3 inflammasome.

ING4 Promotes Stemness Enrichment of Human Renal Cell Carcinoma Cells Through Inhibiting DUSP4 Expression to Activate the p38 MAPK/type I IFN-Stimulated Gene Signaling Pathway.

Renal cell carcinoma (RCC) recurs frequently due to high metastatic spread, resulting in a high mortality. Cancer stem cells play a critical role in initiating the tumor metastasis. Inhibitor of growth 4 (ING4) is a member of the ING family, but its impact on cancer stem cells in RCC is still unknown. In this study, we found that ING4 significantly promoted the sphere-forming size and number of RCC cells under an ultralow-attachment culture condition in vitro, tumor growth and metastasis in vivo, and the expression of some stem-like or pluripotent biomarkers CD44, MYC, OCT4, and NANOG, indicating that ING4 increased the stemness enrichment of RCC cells. Mechanistically, the ING4-activated p38 MAPK pathway possibly upregulated the expression of type I IFN-stimulated genes to promote the formation of RCC stem cells. ING4 could inhibit the expression of DUSP4 to activate p38 MAPK. In addition, selective pharmacological p38 MAPK inhibitors could significantly inhibit stemness enrichment only in ING4-overexpressed RCC cells, suggesting that the p38 MAPK inhibitors might be effective in patients with high ING4 expression in RCC tissue. Taken together, our findings proposed that ING4 might serve as a potential therapeutic target for metastatic RCC, particularly RCC stem cells.

NiCu nanoalloy embedded in N-doped porous carbon composite as superior electrochemical sensor for neonicotinoid determination.

Enhancing catalytic activity is the key to develop electrochemical sensors for monitoring of neonicotinoid such as imidacloprid (IMI), thiamethoxam (THX) and dinotefuran (DNF). Herein, a MOF-derived octahedral NiCu nanoporous carbon composite with abundant N-doped (N/NiCu@C) was synthesized, which was exploited as electrochemical sensor for neonicotinoid determination. Integrating the synergistic effect of NiCu nanoalloy and the hierarchical porous carbon structure, the N/NiCu@C/GCE significantly promoted the diffusion between electrolyte and active site. Meanwhile, the introduction of polyvinylpyrrolidone (PVP) improved the hydrophilicity and dispersibility of N/NiCu@C, endowing superior electrocatalytic performance for IMI, THX and DNF determination, with linear ranges of 0.5-60, 1-60 and 0.5-60 µM, respectively, and detection limits of 0.017, 0.007 and 0.001 µM. Additionally, the sensor can determine IMI, THX and DNF in apples, tomatoes and potatoes with the recovery rate of 92.1-103.4% and RSD ≤ 4.7%. This study has explored a novel modified electrode material for construction of neonicotinoid sensors.

Identification and validation of a cigarette smoke-related five-gene signature as a prognostic biomarker in kidney renal clear cell carcinoma.

Cigarette smoking greatly promotes the progression of kidney renal clear cell carcinoma (KIRC), however, the underlying molecular events has not been fully established. In this study, RCC cells were exposed to the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine) for 120 days (40 passages), and then the soft agar colony formation, wound healing and transwell assays were used to explore characteristics of RCC cells. RNA-seq was used to explore differentially expressed genes. We found that NNK promoted RCC cell growth and migration in a dose-dependent manner, and RNA-seq explored 14 differentially expressed genes. In TCGA-KIRC cohort, Lasso regression and multivariate COX regression models screened and constructed a five-gene signature containing ANKRD1, CYB5A, ECHDC3, MT1E, and AKT1S1. This novel gene signature significantly associated with TNM stage, invasion depth, metastasis, and tumor grade. Moreover, when compared with individual genes, the gene signature contained a higher hazard ratio and therefore had a more powerful value for the prognosis of KIRC. A nomogram was also developed based on clinical features and the gene signature, which showed good application. Finally, AKT1S1, the most crucial component of the gene signature, was significantly induced after NNK exposure and its related AKT/mTOR signaling pathway was dramatically activated. Our findings supported that NNK exposure would promote the KIRC progression, and the novel cigarette smoke-related five-gene signature might serve as a highly efficient biomarker to identify progression of KIRC patients, AKT1S1 might play an important role in cigarette smoke exposure-induced KIRC progression.

Highly selective and sensitive fluorescence detection of tetracyclines based on novel tungsten oxide quantum dots.

Tetracyclines (TCs) residues in animal products have attracted extensive concern due to their potential toxic to human health. Accordingly, it is urgent to develop an efficient method to determine TCs for providing consumers with risk pre-warning. Herein, a novel tungsten oxide quantum dots (WxOy QDs) fluorescence probe for tetracycline (TET) detection was constructed through ethanol-thermal method, which exhibited intense blue fluorescence under 365 nm UV light. Interestingly, blue-emitting WxOy QDs could be quenched obviously after the addition of TET, which may be attributed to the synergism of inner filter effect (IFE), fluorescence resonance energy transfer (FRET) and photo-induced electron transfer (PET). Thereby, the fluorescence method was established for TET detection based on WxOy QDs. Additionally, the presented method was demonstrated by monitoring TET in milk and milk powder with satisfactory recoveries. More importantly, this work offered good demonstration for the detection of food hazard factors.

Construction of a photothermal hydrogel platform with two-dimensional PEG@zirconium-ferrocene MOF nanozymes for rapid tissue repair of bacteria-infected wounds.

Because of increasing antibiotic resistance, careful construction of an efficient phototherm-nanozyme-hydrogel synergistic antibacterial platform is imperative for the treatment of bacteria-infected wounds. In this study, a carrageenan-based hydrogel embedded with polyethylene glycol dicarboxylic acid (COOH-PEG-COOH)-functionalized zirconium-ferrocene metal-organic frames nanosheets (PEG@Zr-Fc MOF hydrogel) was successfully constructed through COOH-PEG-COOH modification and physical assembly. The PEG@Zr-Fc MOF hydrogel could capture Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria through reactive oxygen species (ROS) destruction and kill some bacteria by disintegration of H2O2 into toxic hydroxyl radicals (•OH). Significantly, by introducing the photothermal performance of the PEG@Zr-Fc MOF hydrogel, the catalytic activity of the target material could be improved to achieve a synergistic sterilization effect. The wound infection model experiment confirmed that the PEG@Zr-Fc MOF hydrogel had powerful bactericidal activity and could achieve a rapid tissue repair effect. More importantly, the PEG@Zr-Fc MOF hydrogel had negligible biological toxicity and reduced the risk of inflammation. This study reveals that phototherm-nanozyme-hydrogel synergy holds great potential for bacterial wound infection therapy. Additionally, this is the first study to use two-dimensional MOF nanozymes in combination with hydrogel for antimicrobial therapy. STATEMENT OF SIGNIFICANCE: Bacteria-infected wound is one of the serious threats to public health, and this topic has attracted tremendous attention worldwide in recent decades. Although numerous traditional therapeutic strategies that depend on antibiotics have been developed and applied for treating bacteria-infected wound disease, the effect of wound treatment is becoming increasingly unsatisfactory due to bacterial resistance. The present study provides a feasible method to treat bacterial wound infection by constructing a carrageenan-based hydrogel embedded with polyethylene glycol dicarboxylic acid (COOH-PEG-COOH) functionalized zirconium-ferrocene metal organic frame nanosheets (PEG@Zr-Fc MOF hydrogel). The experiments with the wound infection model confirmed that the PEG@Zr-Fc MOF hydrogel had powerful bactericidal activity and could achieve a rapid tissue repair. This strategy provides a promising avenue to further accelerate the development of antibacterial therapy in biomedical fields.

Multifunctional bacteria-derived tags for advancing immunoassay analytical performance with dual-channel switching and antibodies bioactivity sustaining.

Constructing multifunctional immunochromatographic assays (ICA) carriers with multiple signals and retaining bioactivity of monoclonal antibodies (mAbs) are conducive to the sensitive and accurate point-of-care testing (POCT). To fulfill this pressing need, a microorganism-based microsphere mediated dual-modal ICA (DICA) was developed for sensitive and reliable detection of zearalenone (ZEN). As the key to the biosensor, a superb biotag with an intact coccus morphology was designed based on Staphylococcus aureus biosynthesized quantum dots incorporating Ru(bpy)32+ (SAQDsRu), in which SA offered a specific recognition capacity for Fc region of mAbs, QDs endowed a naked-eye discernible colorimetric signal on the SA, and robust fluorescence signal that remedied for the insufficient brightness of QDs was derived from Ru(bpy)32+. The characterization of SAQDsRu-labeled mAb (SAQDsRu-mAb) probe demonstrated strong luminescence, excellent stability and high affinity with ZEN (affinity constant was approximately 1.723 × 109 M-1), which can significantly improve the detection sensitivity. Impressively, a portable sensing system was developed by the integration of SAQDsRu-DICA with a smartphone-based readout. After optimization, this DICA indicated a limit of detection reaching down to 0.008 ng/mL (colorimetric mode) and 0.0058 ng/mL (fluorescent mode), which were much lower than that of conventional gold nanoparticles-based ICA (0.1029 ng/mL), possessing favorable specificity and repeatability (relative standard deviation (RSD) < 10%). Moreover, the feasibility of the immunoassay was further assessed by measuring ZEN in real samples with satisfactory recoveries, and the results are good consistent with liquid chromatography tandem mass spectrometry (LC-MS/MS).

Surface Selenylation Engineering for Construction of a Hierarchical NiSe2/Carbon Nanorod: A High-Performance Nonenzymatic Glucose Sensor.

As glucose (Glu) is an essential substance for metabolism as well as a symbol to diagnose diabetes, the demand of Glu sensors has increased significantly in recent decades. In this work, a hierarchical Ni-based electrochemical enzyme-free Glu sensor, namely, NiSe2/CNR (carbon nanorod), was engineered through a facile thermal treatment using dimethylglyoxime dinickel salt with selenium (Se) powder. The prepared NiSe2/CNR not only subtly introduces a hierarchical structure with rod-like carbon nanorods and rock-like NiSe2 nanoparticles, which are extremely helpful in offering a greater catalytic activity area and more catalytic active sites, but also incorporates the Se element to increase the inherent activity. The fabricated NiSe2/CNR exhibits distinguished performance for Glu detection in alkaline electrolytes with linear ranges of 0.5-411 µM and 411 µM to 6.311 mM, high sensitivities of 3636 µA mM-1 cm-2 at low concentrations, and 2121 µA mM-1 cm-2 at high concentrations, as well as a low detection limit of 380 nM (S/N = 3). It also possesses favorable reproducibility, stability, and long-term storage capacity. The practical feasibility of NiSe2/CNR was also validated by detecting Glu in human serum. Moreover, the prepared hierarchical NiSe2/CNR is of general interest for the construction of hierarchical Ni-based sensors.

Diverse Dyes-Embedded Staphylococcus aureus as Potential Biocarriers for Enhancing Sensitivity in Biosensing.

Nanomaterials-based immunochromatographic assays (ICAs) have gained great commercial success in real-life point-of-care testing (POCT). Exploring novel carriers of ICAs with improved signaling and sustained activity favors the development of sensitive POCT. Herein a potent signal biotag, colored Staphylococcus aureus (SA), was created for ICA carriers through a mild self-assembly strategy, providing high luminance and abundant specific binding sites for immobilization of monoclonal antibodies (mAbs). The biocompatible SA-dyes (SADs) retained both an intact surface structure for mAbs labeling (Fc portion) and the superior bioactivity of immobilized mAbs (affinity constant was about 109 M-1), thus waiving the intrinsic limitations of traditional nanomaterials and endowing high sensitivity. Proof-of-concept was demonstrated by employing Congo red- or/and fluorescein isothiocyanate-embedded SA (SACR, SAFITC, and SACR-SAFITC) as ICA carriers to detect zearalenone (ZEN) through colorimetric or/and fluorimetric signals. Furthermore, the ICAs satisfied the clinical requirement perfectly, including limit of detection (0.013 ng/mL, which was at least an 85-fold improvement over that of traditional gold nanoparticles-based ICA), linearity (R2 > 0.98), reproducibility (RSD < 8%), selectivity, and stability. Importantly, the proposed biosensors could be well-applied in four real samples for ZEN monitoring with satisfactory recoveries, correlating well with the results from liquid chromatography-tandem mass spectrometry (LC-MS). This work also proved a universal design for tailoring coloration bands for SAD-ICA detection of multiple analytes.

Nicotine-derived NNK induces the stemness enrichment of CRC cells through regulating the balance of DUSP4-ERK1/2 feedback loop.

Cigarette smoking has been considered as an independent risk factor for colorectal cancer (CRC) initiation and progression. In this study, we found that cigarette smoking was significantly associated with poor CRC differentiation (P = 0.040). Since studies have indicated that poorly differentiated tumors are more aggressive and metastasize earlier, leading to poorer prognosis; and cancer stem cells (CSCs) are largely responsible for tumor differentiation state, here we observed that the exposure of nicotine-derived 4-(methylnitrosamino)- 1-(3-pyridyl)- 1-butanone (NNK) promoted cell sphere formation and the expression of the stem cell markers, CD44, OCT4, C-MYC and NANOG in HCT8 and DLD-1 cells. Further colony formation assay, CCK-8 assay and tumor-bearing experiment showed that NNK exposure significantly increased the proliferative and growth ability of CRC cells. In mechanism, we found that NNK-activated ERK1/2 played an important role in enrichment of CRC stem cells and the up-regulation of DUSP4, a major negative regulator of ERK1/2. Moreover, DUSP4 up-regulation was essential for maintaining NNK-activated ERK1/2 in an appropriate level, which was an required event for NNK-induced stemness enrichment of CRC cells. Taken together, our findings provided a possible mechanistic insight into cigarette smoking-induced CRC progression.

Carbon cloth-supported nanorod-like conductive Ni/Co bimetal MOF: A stable and high-performance enzyme-free electrochemical sensor for determination of glucose in serum and beverage.

In this work, we propose a electrochemical enzyme-free glucose sensor by direct growth of conductive Ni/Co bimetal MOF on carbon cloth [Ni/Co(HHTP)MOF/CC] via a facile hydrothermal method. Due to excellent conductivity between Ni/Co(HHTP)MOF and CC, synergic catalytic effect of Ni and Co elements, the Ni/Co(HHTP)MOF/CC not only provides larger surface area and more effective active sites, but also boosts the charge transports and electro-catalytic performance. Under optimized conditions, the Ni/Co(HHTP)MOF/CC shows excellent activity with a linear range of 0.3 µM-2.312 mM, a low detection limit of 100 nM (S/N = 3), a fast response time of 2 s and a high sensitivity of 3250 µA mM-1 cm-2. Furthermore, the Ni/Co(HHTP)MOF/CC was successfully applied for the detection of glucose in real serum and beverages with competitive performances. This facile and cost-effective method provides a novel strategy for monitoring of glucose in biological and food samples.

Macro-meso-microporous carbon composite derived from hydrophilic metal-organic framework as high-performance electrochemical sensor for neonicotinoid determination.

Electrochemical analysis enables pesticides monitoring become rapid and efficient. Herein, novel three dimensional nitrogen-doped macro-meso-microporous carbon composites (N/Cu-HPC) derived from polyvinylpyrrolidone (PVP) doped Cu-metal organic framework were successfully formed via one-pot solvothermal method followed by pyrolysis, which were further applied in high-performance electrochemical determination of neonicotinoid. The introduction of PVP endows the N/Cu-HPC good hydrophilicity preventing aggregation as well as more highly electronegative nitrogen species boosting electro-catalytic property dramatically. Interestingly, the macro-meso-microporous architecture improves mass and charge transports between neonicotinoid molecules and active sites such as Cu nanoparticles and carbon atoms possessing Lewis basicity next to pyridinic-N. Based on the N/Cu-HPC, imidacloprid (IDP), thiamethoxam (THA) and dinotefuran (DNF) were detected with wide linear detection ranges (0.5-60 µM for both IDP and DNF, 1-60 µM for THA) and low detection limits (0.026 µM for IDP, 0.062 µM for THA and 0.01 µM for DNF). Meanwhile, this sensor can be successfully used for determination of IDP, THA and DNF in oat, corn and rice with good recoveries (92.0-100.9%, RSD ≤ 4.8%), demonstrating that the N/Cu-HPC possesses a high potential to be an advanced sensing device for monitoring neonicotinoid in agricultural products.

Metal-polydopamine framework based lateral flow assay for high sensitive detection of tetracycline in food samples.

Gold nanoparticles (AuNPs)-based lateral flow assay (LFA) enables a rapid detection of tetracycline (TET) in food samples but suffers from low sensitivity. Herein, metal-polydopamine framework (MPF), as a label, was employed to load monoclonal antibodies (mAbs) directly as the probe in LFA for highly sensitive sensing of TET. Combining zeolitic imidazolate framework (ZIF-67) and polydopamine (PDA), a stable MPF with large size, well water-dispersible, excellent affinity and optical properties was prepared through a versatile layer-by-layer assembly (LLA) strategy. Under optimized conditions, the biosensor (MPF-LFA) exhibited a great linear relationship in the range of 0.09-6 ng/mL and a detection limit of 0.045 ng/mL for TET detection, which was over 66-fold more sensitive than traditional AuNPs based LFA. Furthermore, the MPF-LFA was successfully applied to the screening of TET in fish, chicken, milk and shrimp samples with satisfied recoveries from 91% to 114%.

Nitrogen, silicon co-doped carbon dots as the fluorescence nanoprobe for trace p-nitrophenol detection based on inner filter effect.

P-nitrophenol (PNP) has been widely applied to industry processing for many purposes, but the persistence and toxicity of residuum may pose risks to human health. To analyze PNP in industrial and agricultural wastewater, a versatile fluorescent probe sensing platform was proposed. In this work, we devised a fluorescence approach that utilized nitrogen, silicon co-doped carbon dots (N,Si-CDs) to monitor PNP originating from the inner filter effect (IFE). The N,Si-CDs were generated in a one-step hydrothermal synthesis, and which possessed outstanding fluorescence signal and water-dispersity. Emission at 441 nm was monitored with excitation at 360 nm using a common spectrofluorometer. The method achieved an exceptionally low limit of detection (LOD) of 0.011 µM. Furthermore, this method not only eliminates the interference from metal ions and acid ions, but also provides a potential application prospect for N,Si-CDs in the field of water monitoring. Analysis of tap and lake water led to 93.30-106.30% recoveries and <1% relative standard deviation at 2.5-25 µM PNP concentrations.

Dual-Emission Zr-MOF-Based Composite Material as a Fluorescence Turn-On Sensor for the Ultrasensitive Detection of Al3.

In this work, a novel zirconium-based metal-organic framework (MOF) composite material, UiO-(OH)2@RhB, has been solvothermally prepared with zirconyl chloride octahydrate, 2,5-dihydroxyterephthalic acid, and rhodamine B (RhB) for ratiometric fluorescence sensing of Al3+ ions in an aqueous medium. The luminescence measurement results showed that, at the single excitation wavelength of 420 nm, the fluorescence intensity of the ligand at 500 nm increased significantly in the case of Al3+, while that of RhB at 583 nm changed slightly, together with an apparent color change. Under optimal conditions, UiO-(OH)2@RhB exhibited an extraordinary sensitivity (10 nM), good selectivity, and a fast response (2 min) for Al3+. As far as we know, the limit of detection is superior to that of the current reported MOF-based Al3+ fluorescence sensors. The response mechanism suggested that -OH could capture Al3+ in water through coordination and high electrostatic affinity and achieved turn-on ratiometric fluorescence through the excited-state intramolecular proton transfer process and stable fluorescence of RhB. In addition, this sensor was also applied to actual food samples (grain beans), with the recoveries ranging from 89.08% to 113.61%. Such a turn-on ratiometric fluorescence sensor will provide a constructive strategy for the ultrasensitive detection of Al3+ in practical applications.

Surface morphology-controllable magnetic covalent organic frameworks: A novel electrocatalyst for simultaneously high-performance detection of p-nitrophenol and o-nitrophenol.

Covalent organic frameworks (COFs) have attracted tremendous interest due to their promising applications, including electrocatalysis originating from their unique structural features. However, it remains a challenge to prepare COFs for p-nitrophenol (PNP) and o-nitrophenol (ONP) electrocatalysis because it is quite difficult to manipulate their dimension, composition, and morphology with abundant active sites. Here, a facile ambient temperature synthesis of unique Fe3O4-based magnetic COFs nanosphere (Fe3O4@AT-COFs) with different surface morphologic structure is reported, which exhibits higher surface area, good water dispersity, long-term stability, excellent electrical conductivity and pre-concentration effect. The prepared Fe3O4@AT-COF-based electrochemical sensor is then directly employed for the simultaneous detection of PNP and ONP with a wide linear detection range of 10-3000 µM and low detection limits (LOD) of 0.2361 µM and 0.6568 µM, respectively. Meanwhile, the Fe3O4@AT-COF can be also well-applied in lake and tap water for monitoring PNP and ONP with outstanding sensitivity and reliability, which is expect to be a high-efficient electrocatalyst with great promise for signal amplification of electrochemical sensing.

miR­3133 inhibits proliferation and angiogenesis by targeting the JUNB/VEGF pathway in human umbilical vein endothelial cells.

Membranous obstruction of the inferior vena cava (MOVC) has the highest incidence rate among the different types of Budd­Chiari syndrome (BCS) in China. The inferior vena cava septum of patients with MOVC contains capillaries and the two surfaces of the membrane are composed of vascular endothelial tissue. Membrane formation occurs due to endothelial damage. MicroRNAs (miRNAs/miRs) have been verified to be involved in the pathogenesis and progression of various human diseases. A previous study by our group suggested that miR­3133 was downregulated in the serum of patients with MOVC. In the present study, the possible mechanistic implication of miR­3133 in MOVC­associated processes was further explored. It was observed that miR­3133 overexpression inhibited, whereas miR­3133 knockdown enhanced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the CCK­8 and tube formation assays. JUNB, a member of activator protein 1 and an important upstream transcriptional molecule of vascular endothelial growth factor (VEGF), was proven to be a direct target gene of miR­3133 using a bioinformatics prediction and luciferase reporter assay. Meanwhile, the mRNA and protein expression of JUNB and VEGF was determined by PCR, ELISA and western blot analyses. Of note, miR­3133 overexpression downregulated, while miR­3133 knockdown elevated the expression of JUNB and VEGF significantly. Furthermore, it was demonstrated that JUNB upregulated the expression and secretion of VEGF to promote HUVEC proliferation and angiogenesis. miR­3133 was able to inhibit the effect of JUNB overexpression to promote cell proliferation, angiogenesis and the expression of VEGF. In conclusion, the present study demonstrated that miR­3133 regulated endothelial cell proliferation and angiogenesis through the JUNB/VEGF pathway, which may provide an approach for inhibiting diaphragm formation of the inferior vena cava in MOVC.

Polydopamine coated zirconium metal-organic frameworks-based immunochromatographic assay for highly sensitive detection of deoxynivalenol.

Conventional immunochromatographic assays (ICAs) based on gold nanoparticles (GNPs) suffer from the disadvantage of low sensitivity. In this work, a highly sensitive ICA based on polydopamine coated zirconium metal-organic frameworks labeled antibodies (ZrPA-Ab) as a novel probe was developed for visual determination of deoxynivalenol (DON). The ZrPA was synthesized via an oxidative self-polymerized assembly (OPMA) strategy using porphyrin functionalized zirconium metal-organic frameworks (Zr-MOFs, MOF-525) and polydopamine (PDA). The Abs could directly attach to the ZrPA surface owing to the large specific surface area, excellent water-stability and bio-compatibility of the ZrPA, on this basis, a sensitive, precise and reliable immunoassay method can be developed for rapid and selective detection of DON. Under optimized conditions, a non-linear calibration curve was obtained in the range of 0-50 ng/mL DON concentration with an IC50 of 1.22 ng/mL, and the visual detection limit was 0.18 ng/mL, which was about 8-times more sensitive than that of the conventional GNPs-based ICA. Finally, the proposed ZrPA-ICA was successfully applied for the detection of DON in pig hind legs meat, green bean, maize and millet samples, revealing the feasible and reliable application of this biosensor in different food matrices. Thus, this work broadens the possibilities for the use of MOFs as a novel labeling carrier in immunoassays.