ZNF503 combined with GATA3 is a prognostic factor in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. Therefore, there is an urgent need to identify prognostic markers to improve current treatment and therapeutic strategies. The transcriptional factor ZNF503 has been reported to promote aggressive breast cancer development through the down-regulation of GATA3 expression and has been identified as a candidate predictive marker. In this study, we explored whether ZNF503 and GATA3 could serve as prognostic markers independently or in combination. We performed a survival analysis of 989 breast cancer patients from The Cancer Genome Atlas (TCGA), and validated the findings in 202 breast cancer patients from tissue microarray (TMA). In TCGA database, the mRNA expression of GATA3 and ZNF503 could not predict TNBC prognosis alone, though the ratio index, ZNF503/GATA3 could be a novel prognostic biomarker in TNBC patients. In TMA database, we detected the protein expression of ZNF503 and GATA3 and found that the combination of the two genes, ZNF503-GATA3, significantly improved the predictive ability of clinical outcomes. The results indicated that the binding index of ZNF503 and GATA3 could be used as a prognostic biomarker in TNBC.</p

Iodide-Switched Deposition for the Synthesis of Segmented Pd–Au–Pd Nanorods: Crystal Facet Matters

Segmented metallic nanorods with well-defined shapes and controllable components play an important role on the systematic investigation of their shape-dependent catalytic, electric, and plasmonic properties of metal nanostructures. Unfortunately, the shape and composition of segmented nanorods are difficult to be precisely controlled via colloidal methods. Here, we reported the growth of Pd–Au–Pd bimetallic heterostructures by using Au 5-fold twinned bipyramids (BPs) as seeds, with KI as a structure-directing reagent. Through a series of control experiments we revealed that two parameters were identified as critical factors for the growth of segmented Pd–Au–Pd nanorods. First, 5-fold twinned Au BPs with low-index end facets and high-index side facets function as a unique template for directed growth. Second, iodide can switch the deposition of Pd on the Au BPs. A high concentration of iodide is believed to block the high-index facets of the Au BPs and lower the reaction kinetics to promote the selective growth of two Pd segments on the Au BPs. As a result, uniformed segmented Pd–Au–Pd nanorods were obtained. The segmented nanorods exhibit intense extinction in the near-IR range and could be a potential candidate for plasmon-based biological applications such as thermal therapy

Simultaneous Preparation of Mesoporous/Macroporous Graphene Aerogels and Bright Green Photoluminescent Graphene Quantum Dots by a Simple Solvothermal Method

In this work, we report a simple one-step solvothermal method using DMF as solvent to fabricate simultaneously mesoporous/macroporous graphene aerogels (GAs) and strong green photoluminescent graphene quantum dots (GQDs). A black monolithic graphene organogel was formed under solvothermal condition and further freeze-dried to obtain GA. In addition, the residual DMF solvent was filtered, dialyzed, and diluted to produce GQDs. The resulting GAs exhibited an average mesopore size of 3.98 nm, while the GQDs had a mean diameter of 4.92 nm. The interconnected macropores were derived from assembled GAs, while the mesopores on GAs were probably formed as a result of “chipping” GQDs off the GA sheets under solvothermal condition. The as-prepared GAs exhibited an amazing adsorption capacity of not only oil products but also toxic solvents like chloroform and toluene. In addition, GAs also showed excellent abilities for dye removal from water. The GQDs exhibited bright green photoluminescent properties with high quantum yield of 11.2%. The solid GQDs were capable of being redissolved in water and most polar organic solvents, and they showed typical excitation- and solvent-dependent properties

Direct Biological Sample Analyses by Laserspray Ionization Miniature Mass Spectrometry

With improved performances, miniature mass spectrometers are becoming suitable for more practical applications. At the same time, the coupling of an approximate ionization source is essential in terms of minimizing sample preparation and broadening the range of samples that could be analyzed. In this study, an atmospheric pressure laserspray ionization (AP-LSI) source was coupled with our home developed miniature ion trap mass spectrometer. The whole system is compact in size, and biological samples could be directly analyzed with minimum sample preparation. Direct detections of peptides, proteins, drugs in whole blood, and urine could be achieved with high sensitivity. The analyses of tissue sections were demonstrated, and different regions in a tissue section could be differentiated based on their lipid profiles. Results suggest that the coupling of AP-LSI with miniature mass spectrometer is a powerful technique, which could potentially benefit target molecule analysis in biological and medical applications

Design of Frustrated Lewis Pairs by Functionalizing N‑Doped Graphene Edge with Tunable Activity for H₂ Dissociation

While the frustrated Lewis pair (FLP) concept has been successfully extended to heterogeneous catalysis, the underlying factors governing the catalytic performances of FLPs and designing strategies remain elusive. Herein, a theoretical study is performed to design metal-free heterogeneous FLPs with tunable activity for hydrogen dissociation. The designed FLPs constructed by functionalizing the N-doped zigzag graphene edge with eight functional groups −BX2 (X = F, Cl, Br, H, CH3, CF3, CN, NO2) can readily heterolytically dissociate H2 (H2 → Hδ− + Hδ+) with reaction barriers varying from 0.15 to 0.70 eV, showing their comparable activity to homogeneous FLPs. More importantly, FLP acidities of designed FLPs are linearly correlated with the reaction energies of H2 dissociation, suggesting the significant role of FLP acidity in determining their catalytic activity. Further calculations show that the reaction barriers of hydrogenation of CO2 also linearly correlate with the reaction energies of H2 dissociation and accordingly are governed by FLP acidity. Overall, this study provides a route for designing metal-free heterogeneous FLPs on graphene materials and discloses a close relationship between the composition (N···BX2), the electronic structure (FLP acidity), and the functionality (catalytic ability) of the FLPs

Interaction of porcine reproductive and respiratory syndrome virus proteins with SUMO-conjugating enzyme reveals the SUMOylation of nucleocapsid protein

<div><p>SUMOylation is a reversible post-translational modification that regulates the function of target protein. In this study, we first predicted by software that the multiple proteins of porcine reproductive and respiratory syndrome virus (PRRSV) could be sumoylated. Next, we confirmed that Nsp1β, Nsp4, Nsp9, Nsp10 and nucleocapsid (N) protein of PRRSV could interact with the sole SUMO E2 conjugating enzyme Ubc9, and Ubc9 could be co-localized with Nsp1β, Nsp4, Nsp9 and Nsp10 in the cytoplasm, while with N protein in both the cytoplasm and nucleus. Finally, we demonstrated that N protein could be sumoylated by either SUMO1 or SUMO2/3. In addition, the overexpression of Ubc9 could inhibit viral genomic replication at early period of PRRSV infection and the knockdown of Ubc9 by siRNA could promote the virus replication. These findings reveal the SUMOylation property of PRRSV N protein and the involvement of Ubc9 in PRRSV replication through interaction with multiple proteins of PRRSV. To our knowledge, this is the first study indicating the interplay between SUMO modification system and PRRSV.</p></div

In Vivo and In Vitro Antiviral Activity of Phlorizin Against Bovine Viral Diarrhea Virus

Bovine viral diarrhea virus (BVDV) is one of the most serious pathogens affecting the cattle industry worldwide. Phlorizin, a kind of flavonoids extracted from apple tree roots, leaves, and fruits, has a variety of biological functions and has been widely used as a herbal supplement and food additive. Here, BALB/c mouse and Madin–Darby bovine kidney (MDBK) cells were used to explore the effect and mechanism of phlorizin against BVDV infection. The results showed that phlorizin significantly inhibited CP BVDV replication and improved the histopathological changes of duodenum and spleen in mice. In vitro studies also confirmed the activity of phlorizin against CP BVDV. Exploration on its potential mechanism suggested that phlorizin inhibited CP BVDV-induced beclin-1 level and the conversion rate of LC3B-I to LC3B-II. Interestingly, although phlorizin also showed a protective effect on MDBK cells, which were treated with 3-methyladenine A (3-MA), the effect was significantly weakened. Furthermore, phlorizin suppressed the stage of BVDV replication but showed no effect on stages of attachment and internalization. Our data further indicated that phlorizin promoted IFN-α and IFN-β levels, decreased IL-1β and IL-6 expression, and regulated RIG-I, MDA5, TLR3, and NLRP3 levels. Similar to CP BVDV results, in vivo and in vitro, phlorizin inhibited NCP BVDV (NY-1 and YNJG2020 strains) infection. These results were the first to be discovered that phlorizin might be used as a new dietary strategy for controlling BVDV infection

The interaction of PRRSV Nsp1β, Nsp4, Nsp9, Nsp10 and N protein with Ubc9.

<p><b>(A)</b> The interaction of Nsp1β, Nsp4, Nsp9, Nps10 and N protein with exogenous Ubc9 by using a Co-IP assay. HEK293 cells were co-transfected with the Myc-Ubc9-expressing plasmid and the HA-Nsp1β-, HA-Nsp4-, HA-Nsp9-, HA-Nsp10- and HA-N-expressing plasmid, respectively. The cell lysates were immunoprecipitated with an anti-HA mAb and probed with anti-HA mAb and anti-Myc PAb. The left panel shows the Co-IP analyses of HA-Nsp1β, HA-Nsp4, HA-Nsp9, HA-Nsp10 and HA-N from cell lysates and the right panel indicates the identification of HA-Nsp1β, HA-Nsp4, HA-Nsp9, HA-Nsp10 and HA-N expressed in cell lysates. The asterisk (★) indicates the IgG light chain band with 26 KDa, and the solid triangle (▲) represents the target protein Myc-Ubc9. <b>(B)</b> The interaction of Nsp1β, Nsp4, Nsp9, Nsp10 and N protein with exogenous Ubc9 by using a GST pull-down assay. The cell lysates containing Nsp1β, Nsp4, Nsp9, Nsp10 and N protein individually were pulled down with prokaryotic expressed and purified GST-Ubc9 protein with an anti-GST mAb and probed with anti-HA and anti-GST mAb. <b>(C)</b> The interaction of Nsp1β, Nsp4, Nsp9, Nsp10 and N protein with endogenous Ubc9. MARC-145 cells were transduced with the lentiviruses that were expressing GFP, Nsp1β, Nsp4, Nsp9, Nsp10, or N individually. The cell lysates were immunoprecipitated with an anti-GFP mAb and followed by Western blot analysis with anti-Ubc9 and anti-GFP antibodies. The left panel indicates the identification of GFP, Nsp1β-GFP, Nsp4-GFP, Nsp9-GFP, Nsp10-GFP and N-GFP expressed in cell lysates, while the right panel shows the Co-IP analyses of GFP, Nsp1β-GFP, Nsp4-GFP, Nsp9-GFP, Nsp10-GFP and N-GFP from cell lysates.</p