Integrated analysis of bulk and single-cell RNA sequencing reveals the interaction of PKP1 and tumor-infiltrating B cells and their therapeutic potential for nasopharyngeal carcinoma.

Immunotherapy is an individualized therapeutic strategy for nasopharyngeal carcinoma (NPC). However, few molecular targets are clinically satisfactory. This work aimed to integrate bulk and single-cell RNA sequencing data to identify novel biomarkers involved in NPC. We performed differentially expressed gene (DEG) analysis, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and immune cell infiltration analysis prior to correlation analysis of the identified genes and immune cells and further assessed the prognostic effects of the biomarkers and immune cells in NPC. As a result, PKP1, a potential molecular biomarker associated with immune infiltration, and tumor-infiltrating lymphocyte-B cells (TIL-Bs) were identified as promising therapeutic targets for NPC. Importantly, immunohistochemistry (IHC) validated that PKP1 protein expression was mainly found in NPC cells rather than noncancerous cells. In addition, the tumor microenvironment (TME) of NPC was characterized by the infiltration of more dendritic cells (DCs) and γδT cells but fewer B cells. Our results suggest that the interaction of PKP1 and TIL-B cells is involved in NPC development. It is possible that TIL-B cells produce immunoglobulin G (IgG) to tumor antigens, such as PKP1, or viral antigens, including EBV and HPV, to execute antitumor ability through DC and T cells. In response, NPC cells express proteins such as PKP1 (absent in normal nasopharynx) to induce myeloid-derived suppressor cell (MDSC) expansion, which subsequently impairs the proliferation of B cells and results in B-cell death by generating iNOS and NOX2. In summary, our findings provide a potential therapeutic strategy for NPC by disrupting the interaction of PKP1 and TIL-Bs in the TME.

Bio-Inspired Passion Fruit-like Fe3O4@C Nanospheres Enabling High-Stability Magnetorheological Performances.

Magnetorheological (MR) fluids have been successfully utilized in versatile fields but are still limited by their relatively inferior long-term dispersion stability. Herein, bio-inspired passion fruit-like Fe3O4@C nanospheres were fabricated via a simple hydrothermal and calcination approach to tackle the settling challenge. The unique structures provide sufficient active interfaces for the penetration of carrier mediums, leading to preferable wettability between particles and medium oils. Compared with the bare Fe3O4 nanoparticle suspension, the resulting Fe3O4@C nanosphere-based MR fluid exhibits desirable stability and relatively low field-off viscosity even at a high particle concentration up to 35 vol %.

Comparisons between ticagrelor and clopidogrel following percutaneous coronary intervention in patients with acute coronary syndrome: a comprehensive meta-analysis.

BACKGROUND: The efficacy and safety of ticagrelor following percutaneous coronary intervention for patients with acute coronary syndrome remains unclear. This study sought to evaluate clinical outcomes of ticagrelor as part of dual-antiplatelet treatment for these patients. METHODS: PubMed, MEDLINE, Embase, and other Internet sources were searched for eligible citations. The primary end point was major adverse cardiovascular and cerebrovascular events, consisting of cardiovascular death, myocardial infarction, and stroke. The secondary end point was the occurrence of definite/probable stent thrombosis (ST). The risk of bleeding was chosen to be the safety end point. RESULTS: Eleven clinical trials - six randomized trials and five observational trials - were finally analyzed. A tendency toward reduction in the risk of major adverse cardiovascular and cerebrovascular events was observed only with respect to ticagrelor (OR 0.83, 95% CI 0.66-1.03; P=0.091), which might have resulted from the lower risk of cardiovascular death (OR 0.78, 95% CI 0.68-0.89; P<0.001). The overall incidence of ST differed significantly between the ticagrelor group and the clopidogrel group (OR 0.74, 95% CI 0.59-0.93; P=0.009), but the risk of bleeding, regardless of major or minor bleeding, increased significantly. CONCLUSION: As part of dual-antiplatelet treatment following percutaneous coronary intervention, ticagrelor significantly reduced the risk of cardiovascular death and ST in acute coronary syndrome patients, but at the cost of bleeding. More powerful relevant randomized trials are still warranted to guide clinical decision-making.

Recent progress in two-dimensional inorganic quantum dots.

The development of two-dimensional (2D) inorganic materials-based quantum dots (QDs) is still in its infancy but is triggering immense enthusiasm due to their high chemical stability, good aqueous dispersibility, excellent optical property, good biocompatibility and easy functionalization. This review covers almost all the extant 2D-QDs based on graphene, phosphorene, silicene, carbides, nitrides, transition metal dichalcogenide, transition metal oxides and MXenes, etc. Their categories, synthetic routes, properties, functionalization and applications are critically highlighted. In the application section, special emphasis is placed on the progress in bioimaging, cancer therapy, fluorescent sensing and optoelectronics. Meanwhile, the latest advances in 2D QDs-based catalysis and energy since 2015 are addressed. Moreover, 2D nanoclusters, in particular 2D-QDs, are also included. This review provides guidance for 2D-QDs studies to meet the increasing demands in the many diverse applications.

Fabrication of smart magnetite/reduced graphene oxide composite nanoparticles and their magnetic stimuli-response.

Novel Fe3O4/reduced graphene oxide (RGO) composite nanoparticles were synthesized and confirmed by FT-IR spectra as good candidates for magnetic stimuli-responsive magnetorheological (MR) materials. The morphology of Fe3O4/RGO was observed by both scanning and transmission electron microscopy and their sedimentation stability improved due to a decreased density of the synthesized composites. The MR performance of the Fe3O4/RGO-based fluid was investigated with a rotational rheometer, and the Cho-Choi-Jhon model of the rheological equation of state was adopted to explain their performances for the entire shear rate region.

Celebrating Soft Matter's 10th anniversary: stimuli-responsive Pickering emulsion polymerized smart fluids.

The Pickering emulsion process is an important and interesting way of forming hybrid soft matter particles stabilized by solid particles as surfactants instead of the extensive use of conventionally available organic surfactant molecules. This Highlight briefly reviews stimuli-responsive polymer/inorganic hybrid materials fabricated by Pickering emulsion polymerization along with the rheological characteristics of their electrorheological and magnetorheological smart fluids under electric and magnetic fields, respectively.

Graphene oxide based smart fluids.

Graphene oxide (GO), a graphene-related material containing oxygen-functional groups, has attracted considerable attention because of its strongly hydrophilic behavior and potential use in GO-hybrid composites. We put our focus on the fabrication and rheological characteristics of GO-based electrorheological and magnetorheological smart fluids under electric and magnetic fields, respectively in this Highlight. A brief perspective on the significant role of GO in tribology and the amphiphilic characteristics of Pickering emulsions are also included.

Different routes lead to apoptosis in unfertilized sea urchin eggs.

Results obtained in various species, from mammals to invertebrates, show that arrest in the cell cycle of mature oocytes is due to a high ERK activity. Apoptosis is stimulated in these oocytes if fertilization does not occur. Our previous data suggest that apoptosis of unfertilized sea urchin eggs is the consequence of an aberrant short attempt of development that occurs if ERK is inactivated. They contradict those obtained in starfish, another echinoderm, where inactivation of ERK delays apoptosis of aging mature oocytes that are nevertheless arrested at G1 of the cell cycle as in the sea urchin. This suggests that the cell death pathway that can be activated in unfertilized eggs is not the same in sea urchin and in starfish. In the present study, we find that protein synthesis is necessary for the survival of unfertilized sea urchin eggs, contrary to starfish. We also compare the effects induced by Emetine, an inhibitor of protein synthesis, with those triggered by Staurosporine, a non specific inhibitor of protein kinase that is widely used to induce apoptosis in many types of cells. Our results indicate that the unfertilized sea urchin egg contain different mechanisms capable of leading to apoptosis and that rely or not on changes in ERK activity, acidity of intracellular organelles or intracellular Ca and pH. We discuss the validity of some methods to investigate cell death such as measurements of caspase activation with the fluorescent caspase indicator FITC-VAD-fmk or acidification of intracellular organelles, methods that may lead to erroneous conclusions at least in the sea urchin model.

Core-Shell Structured Electro- and Magneto-Responsive Materials: Fabrication and Characteristics.

Core-shell structured electrorheological (ER) and magnetorheological (MR) particles have attracted increasing interest owing to their outstanding field-responsive properties, including morphology, chemical and dispersion stability, and rheological characteristics of shear stress and yield stress. This study covers recent progress in the preparation of core-shell structured materials as well as their critical characteristics and advantages. Broad emphasises from the synthetic strategy of various core-shell particles to their feature behaviours in the magnetic and electric fields have been elaborated.

Facile and fast synthesis of polyaniline-coated poly(glycidyl methacrylate) core-shell microspheres and their electro-responsive characteristics.

Electro-responsive core-shell structured particles were fabricated in two steps. In the first step, a spherical and monodisperse poly(glycidyl methacrylate) (PGMA) core was prepared by dispersion polymerization with an epoxy group, which was then functionalized with an amine functional group (ami-PGMA) via an epoxide-amine reaction with ethylenediamine. In the second step, a conducting polyaniline (PANI) shell was grafted onto the ami-PGMA surface via the in situ polymerization of an aniline monomer with a uniform thickness. The epoxy group on the PGMA microspheres provided a simple and fast way to react with amine functional groups without the need for a further swelling or grafting process. The morphology of the core-shell structure was confirmed by scanning election microscopy and transmission electron microscopy. The electrorheological properties of the PGMA/PANI particles-based suspension were examined using a Couette-type rotational rheometer under an applied electric field. The shear stress curves were fitted to the Cho-Choi-Jhon (CCJ) model of the rheological equation of state.

Electrorheology of graphene oxide.

Novel polarizable graphene oxide (GO) particles with oxidized groups on their edge and basal planes were prepared by a modified Hummers method, and their electro-responsive electrorheological (ER) characteristics when dispersed in silicone oil were examined with and without an electric field applied. The fibrillation phenomenon of this GO-based electro-responsive fluid was also observed via an optical microscope under an applied electric field. Both flow curves and dielectric spectra of the ER fluid were measured using a rotational rheometer and a LCR meter, respectively. Its viscoelastic properties of both storage and loss moduli were also examined using a vertical oscillation rheometer equipped with a high voltage generator, finding that the GO-based smart ER system behaves as a viscoelastic material under an applied electric field.

Silica-graphene oxide hybrid composite particles and their electroresponsive characteristics.

Silica-graphene oxide (Si-GO) hybrid composite particles were prepared by the hydrolysis of tetraethyl orthosilicate (TEOS) in the presence of hydrophilic GO obtained from a modified Hummers method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images provided visible evidence of the silica nanoparticles grafted on the surface of GO, resulting in Si-GO hybrid composite particles. Energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) spectra indicated the coexistence of silica and GO in the composite particles. The Si-GO hybrid composite particles showed better thermal stability than that of GO according to thermogravimetric analysis (TGA). The electrorheological (ER) characteristics of the Si-GO hybrid composite based ER fluid were examined further by optical microscopy and a rotational rheometer in controlled shear rate mode under various electric field strengths. Shear stress curves were fitted using both conventional Bingham model and a constitutive Cho-Choi-Jhon model. The polarizability and relaxation time of the ER fluid from dielectric spectra measured using an LCR meter showed a good correlation with its ER characteristics.

Fast and facile fabrication of a graphene oxide/titania nanocomposite and its electro-responsive characteristics.

A graphene oxide/titania (GO/TiO(2)) nanocomposite was fabricated by a facile electrostatic attraction method. With high polarization of GO particles and a relatively high dielectric constant of TiO(2) nanoparticles, the GO/TiO(2) nanocomposite is observed to be a potential electro-responsive electrorheological material under an applied electric field.

Stage-associated dynamic activity profile of transcription factors in nasopharyngeal carcinoma progression based on protein/DNA array analysis.

Transcription factors (TFs) are crucial modulators of gene regulation during the development and progression of tumors. We previously reported the activation of TFs in nasopharyngeal carcinoma (NPC) cell lines. In this study, we explored the activity profiles of TFs in Protein/DNA array data of a 12-tissue independent set and a 13-tissue pooled set of NPC that included different clinical stages. TFs associated with tumor progression were revealed using a generalized linear model-based regression analysis. Immunohistochemical analysis of clinical NPC samples was used to validate the results of array analysis. We identified 26 TFs that showed increased activities. Of these 26 TFs, 16 were correlated with clinical stages. Activity changes of AP2 and ATF/CREB were confirmed by electrophoretic mobility shift assay (EMSA), and increased expression of AP2α, ß, γ, ATF2, and ATF1 in nuclei of tumor cells was associated with clinical stages. In addition, the expressions of AP2α, ATF2, and ATF1 were correlated with those of their target genes (epithelia growth factor receptor (EGFR) and matrix metalloproteinase 2 (MMP-2), respectively). This study provides data and valuable clues that can be used to further investigate the laws of gene transcription regulation in NPC and to identify suitable targets for the development of TF-targeted antitumor agents.

Colloidal graphene oxide/polyaniline nanocomposite and its electrorheology.

A nanocomposite of colloidal graphene oxide (CGO) and polyaniline (PANI) was fabricated via in situ oxidation polymerization in the presence of CGO prepared via a modified Hummers method without a dopant, in which the graphene oxide was individually exfoliated. Its electrorheological properties and other physical characteristics were studied.

[Survey of the evolutionary characteristics of influenza H1N1 hemagglutinin gene HA1 in 2000-2009].

OBJECTIVE: To study the global evolutionary characteristics of hemagglutinin gene HA1 of influenza H1N1 infecting different species during 2000-2009. METHODS: The target sequences were downloaded from NCBI and analyzed using bioinformatic software to construct the phylogenetic tree. RESULTS: The HA1 amino acid sequences of influenza H1N1 contained four mutated antigenic sites and receptor-binding sites, and the novel influenza virus shared most of the mutated amino acid sites with swine H1N1 influenza virus. CONCLUSION: The HA1 gene of novel influenza virus might originate from the early swine H1N1 influenza virus from North America, and in the evolutionary process, a number of important sites of HA1 gene mutated to result in the outbreak of influenza.

Identification of a new seven-span transmembrane protein: NGX6a is downregulated in nasopharyngeal carcinoma and is associated with tumor metastasis.

Nasopharyngeal carcinoma (NPC)-associated gene 6 (NGX6) is a novel candidate metastasis suppressor gene that can significantly decrease the growth, motility, and invasion of NPC cells. In this study, we generated a highly specific NGX6 polyclonal antibody and analyzed its distribution in the human fetus by Western blot and immunohistochemistry. The result of the Western blot showed the protein of NGX6 had two types of isoforms, isoform a (NGX6a) and isoform b (NGX6b). Isoform a is composed of 472 amino acids with a calculated molecular mass of 52 kDa, whereas isoform b is composed of 338 amino acids with a calculated molecular mass of 37 kDa. It is predicated that there is an epidermal growth factor domain in the N terminal of both a and b isoforms, and seven transmembrane domains in NGX6a, but only two transmembrane domains in NGX6b. The expression level of NGX6a was higher than that of NGX6b in human fetal tissue. Obvious high expression of NGX6a protein presents in the nervous system and epithelial tissues of the human fetus, but the NGX6b protein (37 kDa) is mainly expressed in the nervous system. We further analyzed the tissue microarray, which contained 154 NPC biopsies and 70 non-NPC biopsies, and found that NGX6a was significantly downregulated in NPC and associated with tumor metastasis.

[Construction of a recombinant lentiviral expression vector carrying carcinoembryonic antigen gene and its expression in dendritic cells].

OBJECTIVE: To construct a lentiviral expression vector of human carcinoembryonic antigen (CEA), and identify its expression in dendritic cells (DCs). METHODS: Human CEA-encoding sequence was amplified, purified, ligated with lentiviral vector plasmid pLentiGFP and verified by sequencing. The verified recombinant vector plasmid (pLentiGFP-CEA), the packaging plasmid p 8.2 and pVSV-G were transfected into 293T cells by Lipofectamine(TM) 2000 reagent. The supernatant of the cultured 293T cells was collected to infect the DCs. The expression of CEA in the transfected DCs was assayed by RT-PCR and Western blotting. RESULTS: CEA lentiviral vector was highly expressed in the transfected DCs as observed using fluorescence microscope 48 h after the the transfection. The human CEA gene was successfully amplified by RT-PCR with a length of about 2100 bp. Western blotting also showed CEA expression in the transfected DCs. CONCLUSION: The human CEA lentiviral expression vector has been successfully constructed and the functional CEA protein can be expression in the transfected DCs. This facilitates further studies of the function of CEA at the molecular level.

Gene expression profiling of nasopharyngeal carcinoma reveals the abnormally regulated Wnt signaling pathway.

Nasopharyngeal carcinoma (NPC) is a particularly common malignant disease in areas of south China and Southeast Asia. To characterize the gene expression profiling of NPC, we detected the gene expression profiles in 22 NPC and 10 nontumor nasopharyngeal epithelial tissues by complementary DNA microarray. We identified 503 genes that were significantly (P < .001) differentially regulated between NPC and nontumor nasopharyngeal epithelial tissues. The differentially expressed genes are involved in many signaling pathways, such as the Wnt, transforming growth factor-beta, and mitogen-activated protein kinase signaling pathways. The aberrant expression of the Wnt signaling pathway components, such as wingless-type MMTV integration site family, member 5A, Frizzled homolog 7, casein kinase IIbeta, beta-catenin, CREB-binding protein, and Dishevelled-associated activator of morphogenesis 2 was validated on the NPC tissue microarrays. The data suggest that the Wnt signaling pathway may be abnormally regulated in NPC, which provides insight into the molecular mechanisms of NPC.