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In this study, a sensitive high-performance liquid chromatography method for zearalenone determination in feeds and grains was established based on the automatic immunomagnetic bead purifier analyzer (KY-AMI-I) for the one-step sample pre-treatment. Various parameters that may affect the analytical performance were investigated. Immunomagnetic bead separation system based on a monoclonal antibody (anti-ZEN antibody-immunomagnetic beads conjugation) was individually prepared for the ZEN purification. Besides, the average recoveries in spiked samples ranged from 75.23 to 102.62%, and the relative standard deviations were between 3.55 and 8.07% (

Organic luminogens with room temperature phosphorescence (RTP) have been paid great attention and developed rapidly for their wide application values. Until now, the internal mechanism and source of phosphorescence are still obscure, especially for the relationship between molecular dimer and RTP emission. Hence, we designed and synthesized eight phenothiazine 5,5-dioxide derivatives to directly reveal how the monomer and dimer in packing affect the RTP behavior. Dimers with strong π-π stacking (θ d θ d

Lysosomes have fundamental physiological roles and have previously been implicated in Parkinson’s disease1–5. However, how extracellular growth factors communicate with intracellular organelles to control lysosomal function is not well understood. Here we report a lysosomal K+ channel complex that is activated by growth factors and gated by protein kinase B (AKT) that we term lysoKGF. LysoKGF consists of a pore-forming protein TMEM175 and AKT: TMEM175 is opened by conformational changes in, but not the catalytic activity of, AKT. The minor allele at rs34311866, a common variant in TMEM175, is associated with an increased risk of developing Parkinson’s disease and reduces channel currents. Reduction in lysoKGF function predisposes neurons to stress-induced damage and accelerates the accumulation of pathological α-synuclein. By contrast, the minor allele at rs3488217—another common variant of TMEM175, which is associated with a decreased risk of developing Parkinson’s disease—produces a gain-of-function in lysoKGF during cell starvation, and enables neuronal resistance to damage. Deficiency in TMEM175 leads to a loss of dopaminergic neurons and impairment in motor function in mice, and a TMEM175 loss-of-function variant is nominally associated with accelerated rates of cognitive and motor decline in humans with Parkinson’s disease. Together, our studies uncover a pathway by which extracellular growth factors regulate intracellular organelle function, and establish a targetable mechanism by which common variants of TMEM175 confer risk for Parkinson’s disease. The identification of a lysosomal K+ channel complex—comprising AKT and the pore-forming TMEM175—provides insights into the mechanisms through which variants of the pore-forming protein affect the development of Parkinson’s disease.

A novel fluorescent sensor based on bovine serum albumin stabilized gold/silver nanoclusters (BSA-Au/Ag NCs) was developed for sensitive and facile detection of alkaline phosphatase (ALP) activity. For this fluorescent sensor, ascorbic acid 2-phosphate (AAP) was decomposed into ascorbic acid (AA) and phosphate by catalysis with ALP. The initial red fluorescence of the BSA-Au/Ag NCs was effectively quenched by KMnO4 and then the fluorescence was recovered by addition of AA. The mechanism of interaction between BSA-Au/Ag NCs and KMnO4 and AA was studied with use of the fluorescence lifetime and UV-vis absorption spectra. The results indicated that the oxidation/reduction modulated by KMnO4/AA led to surface structure destruction/restoration of the BSA-Au/Ag NCs, resulting in fluorescence quenching/recovery. The proposed fluorescence-based method based on a dark background was used to detect ALP and had excellent sensitivity, with a detection limit of 0.00076 U/L. Moreover, the method was applied to the determination of added analytes, with satisfactory recoveries (97.0–105.0 %). In a simulated eutrophic water body, this method successfully detected ALP in actual water samples and could monitor the dynamic changes of ALP activity through visual observation. More importantly, the proposed fluorescent sensor not only has the advantages of simple operation and high sensitivity but has also been successfully used on filter paper to establish a rapid and visual test paper for ALP.

The Shuangwang gold deposit, located in the Fengxian-Taibai fore-arc basin in the western Qinling Orogen of Central China, has yielded over 70 tons of gold. It is an orogenic gold deposit occurring in an NW-trending breccia belt. Most of the ores are hydrothermal breccia type containing fragments of adjacent strata cemented by ankerite and pyrite. Pyrite is the most abundant metallic mineral and the major gold-bearing mineral in the ores. A total of 58 pyrite samples from main ore bodies of the Shuangwang gold deposit have been analysed for 44 trace elements by HR-ICP-MS. Sb, Ba, Cu, Pb, Zn, Bi, Mo, Co are selected as indicator elements to investigate the potential usefulness of trace elements in pyrite as an indicator in gold exploration. The results show that the supra-ore halo elements Sb and Ba, which may have been more active than other near-ore halo elements and sub-ore halo elements, are best to characterize the shape of ore bodies. Five target areas are pointed out for deep ore exploration based on a comprehensive study of supra-ore, near-ore and sub-ore halos. This study provides evidence that trace elements in pyrite can be used to depict the deep extension of ore bodies and to vector towards undiscovered ore bodies.

The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4+ and CD8+ T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA. Twenty-eight out of 38 cancer specimens exhibited NY-ESO-1 protein expression, 2/38 showed a strong universal (4+) NY-ESO-1 staining, and 9/40 cancer lesions exhibited a strong (4+) staining for survivin. We could detect antigen-specific IFN-γ responses in 25% blood samples for NY-ESO-1 and 30% for survivin. NY-ESO-1-expanded T-cells recognized naturally processed and presented epitopes. NY-ESO-1 or survivin expression in glioma represents viable targets for anticancer-directed T-cells for the biological therapy of patients with glioma. Electronic supplementary material The online version of this article (doi:10.1007/s00262-017-2066-z) contains supplementary material, which is available to authorized users.

The objective of this study is to characterize the relationship between forkhead box C2 protein (Foxc2) and leptin under adipose inflammatory response.Lipopolysaccharide (LPS)-induced inflammatory model was conducted. Data from wild-type and ob/ob mice were used to compare the alternative role of leptin on Foxc2-mediated inflammation and browning. Transcriptional regulation and protein-protein interaction were analyzed by bioinformatics and proved by chromatin immunoprecipitation and co-immunoprecipitation experiment.Foxc2 and leptin correlated with inflammation and browning of white adipose tissue (WAT) in LPS-treated mice. Moreover, Foxc2-mediated inhibition of inflammation involved downstream activation of leptin signal and promoted WAT browning. We then determined CREB, the potential transcriptional factor of leptin, was required for Foxc2-mediated inflammation in the regulation of WAT browning. Foxc2 alleviated adipocyte inflammation by reducing leptin-mediated Janus-activated kinase 2/signal transducer and activator of transcription 3 (STAT3) pathway. Importantly, STAT3 physically interacted with PRDM16 and formed a complex to promote WAT browning. Exogenous Foxc2 overexpression also ameliorated inflammation and promoted adipose browning in high fat diet (HFD)-induced obese mice.Our results indicated that Foxc2 inhibited inflammation and promoted browning of WAT through positive regulation of leptin signal and the STAT3-PRDM16 complex. These findings identify a new potential means to prevent and treat obese caused metabolic syndrome of mammals.

Multiwalled carbon nanotubes (MWCNT) were covered with reduced graphene oxide nanoribbons (rGONR) to give a material with a core-shell heterostructure of the type MWCNT@rGONR. It was obtained by (a) longitudinal partial unzipping of MWCNT to form MWCNT@GONR, and (b) subsequent chemical reduction with hydrazine to give MWCNT@rGONR. The MWCNT@rGONR heterostructure was used to modify a glassy carbon electrode (GCE) to obtain an electrochemical sensor for p-dihydroxybenzene (DHB). The synergistic effects of the MWCNT and the rGONR results in a distinctly improved redox current towards DHB compared to a bare GCE, an MWCNT/GCE, and an MWCNT@GONR/GCE. At the working voltage range from −100 to 400 mV, it displays a linear response to DHB in the 80 to 3000 nM concentration range with a 20 nM detection limit.

In order to investigate the mechanism of suppressor of cytokine signaling 2 (SOCS2) on mitochondrial biogenesis, RNA interference and over-expression plasmid vectors of SOCS2 were used to transfect murine skeletal muscle C2C12 cells. Results demonstrated that over-expression of SOCS2 inhibited the differentiation of C2C12 cells, and reduced the expression of MyHC, MyoD and MyoG while elevated the protein expression of MSTN. Meanwhile the expression of PGC-1α, MDH, CPT-1 were significantly elevated in the RNA interference of SOCS2 group which were decreased in SOCS2 overexpression group. However, there was no change on the expression of UCP1 in both two groups. JC-1 dyeing showed overexpression of SOCS2 decreased the mitochondrial membrane potential and results of immunofluorescence, real-time PCR and western blotting indicated the increase expression of Cyt c, while interference SOCS2 had the opposite effects in C2C12 cells. Moreover, interference of SOCS2 elevated the p38 phosphorylation level then further increased the phosphorylation of ATF2, whereas overexpression of SOCS2 alleviated this phenomenon. Taken together, our observations indicated that SOCS2 could suppress myotube formation, act as an anti-regulator of mitochondria biogenesis via inhibiting p38 MAPK signal pathway.

An enzyme-linked immunosorbent assay (ELISA) was developed based on a polyclonal antibody for the analysis of thiacloprid in agricultural samples. Thiacloprid hapten was synthesized and conjugated to bovine serum albumin to produce an immunogen and ovalbumin to produce a coating antigen. Polyclonal antibodies were obtained from immunized New Zealand white rabbits. Under optimal conditions (5 % methanol, 0.1 mol/L Na+, pH 5.5), the ELISA showed a 50 % inhibitory concentration (IC50) value of 0.01 mg/L and a limit of detection (IC10) of 0.47 μg/L. No obvious cross-reaction with the other structural analogs of neonicotinoid insecticides showed that the polyclonal antibodies had a high specificity for thiacloprid. The average recoveries from spiked water, soil, pear, and tomato were in the range of 80 to 119 %. The results of the ELISA were confirmed by high-performance liquid chromatography, and the correlation of the results from the two methods had a high correlation coefficient of 0.99 (n = 3) in spiked samples (soil, pear, and tomato). The proposed ELISA could successfully be applied to the determination of thiacloprid residues in agricultural samples.

Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca2+ level. Further analysis revealed that adiponectin alleviated ER stress-induced adipocyte apoptosis by elevating peroxisome proliferator-activated receptor alpha (PPARα) mRNA level. Our data also confirmed that adiponectin reduced early apoptotic cells and blocked the mitochondrial apoptosis pathway by activating the AdipoR1/AMP-activated protein kinase (AMPK) signal pathway. In addition, PPARα bound to ATF2 promoter region and inhibited transcription of ATF2. The inhibition of adipocyte apoptosis by adiponectin was correlated with transcriptional suppression of ATF2. Furthermore, adiponectin inhibited ER stress-induced apoptosis by activating the AMPK/PKC pathway. In summary, our data demonstrate adiponectin inhibited ER stress and apoptosis of adipocyte in vivo and in vitro by activating the AMPK/PPARα/ATF2 pathway. Our study establishes that adiponectin is an important adipocytokine for preventing and treating obesity.