Highly Interfacial Active Gemini Surfactants as Simple and Versatile Emulsifiers for Stabilizing, Lubricating and Structuring Liquids.

To date, locking the shape of liquids into non-equilibrium states usually relies on jamming nanoparticle surfactants at an oil/water interface. Here we show that a synthetic water-soluble zwitterionic Gemini surfactant can serve as an alternative to nanoparticle surfactants for stabilizing, structuring and additionally lubricating liquids. By having a high binding energy comparable to amphiphilic nanoparticles at the paraffin oil/water interface, the surfactant can attain near-zero interfacial tensions and ultrahigh surface coverages after spontaneous adsorption. Owing to the strong association between neighboring surfactant molecules, closely packed monolayers with high mechanical elasticity can be generated at the oil/water interface, thus allowing the surfactant to produce not only ultra-stable emulsions but also structured liquids with various geometries by using extrusion printing and 3D printing techniques. By undergoing tribochemical reactions at its sulfonic terminus, the surfactant can endow the resultant emulsions with favorable lubricity even under high load-bearing conditions. Our study may provide new insights into creating complex liquid devices and new-generation lubricants capable of combining the characteristics of both liquid and solid lubricants.

Dual-Driven Mechanically and Tribologically Adaptive Hydrogels Solely Constituted of Graphene Oxide and Water.

Although mythologies and fictions have recorded living creatures fully composed of inorganics, it is however hard to turn inorganic constituents into lifelike materials in reality as they usually do not possess characteristics required for constructing a living organism. Here, we report to our knowledge the first biomimetic hydrogel in response to both pH and temperature variations that solely comprises graphene oxide and water. The hydrogel is capable of abruptly and reversibly switching its mechanical and tribological properties by more than 10-fold and 5-fold magnitudes, respectively, as a result of pH- and/or thermal-induced topological reconfiguration of its internal microstructure and ordering. Such behavior closely mimics some natural living organisms such as muscles and sea cucumbers. The hydrogel also shows a low coefficient of friction at pH 2 and room temperature, indicating it a potent smart lubricant free of any flammable and toxic organic base oils and additives.

Spectroscopic Investigation and Nanoscale Characterization of Epinephrine Autooxidation under Alkaline Conditions.

Melanins are intriguing biomaterials with unique physical and chemical properties. Due to the insoluble nature of the synthetic melanins prepared from different precursors, such as 3,4-dihydroxy-phenylalanine (DOPA) and dopamine (DA), it is still challenging to reveal the structure-property relationships. In this work, the autoxidation of epinephrine (EP) under basic conditions was investigated from the perspective of supramolecular chemistry, and the formed soluble epinephrine-melanin (EPM) was characterized on the nanoscale. The supramolecular aggregate nature of oxidation products has been identified on the basis of spectroscopic investigations. A two-dimensional sheet-like morphology with highly ordered in-plane stacking structures was observed for the first time, and the thickness of the nanosheet increased with increasing EPM concentration. More importantly, in contrast to the well-known monotonic absorption profiles of synthetic melanins, EPM shows featured and unusual pH-responsible absorption profiles in the near-ultraviolet region (UVA). The decrease in pH can induce the disappearance of the absorption in the lower-energy band and the reduction of aggregate size. The oxidative and aggregation kinetic processes of EP were investigated in three different alkaline systems by the combination of absorption and fluorescence spectroscopies. The oxidation process of EP shows concentration- and buffer-dependent behaviors. The unusual absorption properties of EPM were exploited for the fabrication of transparent UV-shielding chitosan biofilms and gelatin hydrogels. Extensive research on the molecular structures, supramolecular exciton coupling, and material-oriented property exploitation of EPM is highly anticipated.

An electrochemiluminescence immunosensor for the N-terminal brain natriuretic peptide based on the high quenching ability of polydopamine.

A sandwich-type electrochemiluminescence (ECL) immunosensor for the N-terminal brain natriuretic peptide (NT-proBNP) is described. The assay is based on the quenching of the ECL of graphite-like carbon nitride (g-C3N4) by polydopamine (PDA). Two-dimensional g-C3N4 is grown in-situ on titanium dioxide nanoflowers (TiO2 NFs). The macroporous structure of the NFs enhances the interfacial stability of g-C3N4, and also promotes the ECL reaction of g-C3N4 with the co-reactant. The introduction of gold nanoparticles into the matrix further enhances the ECL and facilitates the immobilization of capture antibodies. The nanoquencher used to label the secondary antibody is synthesized by catalytic polymerization of dopamine in the presence of bimetallic NiPd nanoparticles. The nanoquencher preserves the high reactivity of polydopamine and quenches the ECL of the g-C3N4/TiO2 system. Compared to other methods, the detection limit for NT-proBNP is decreased to 50 fg∙mL-1. Graphical abstract Schematic presentation of the electrochemiluminescence (ECL) process of the immunosensor: titanium dioxide nanoflowers@graphite-like carbon nitride-gold nanoparticles (TiO2 NFs@g-C3N4-Au) as luminophor, and polydopamine (PDA) as nanoquencher.

Biophysical impact of lubricating base oil aerosols on natural pulmonary surfactant film.

Lubricating base oils have been extensively employed for producing various industrial and consumer products. Therefore, their environmental and health impacts should be carefully evaluated. Although there have been many reports on pulmonary cytotoxicity and inflammatory responses of inhaled lubricating base oils, their potential influences on pulmonary surfactant (PS) films that play an essential role in maintaining respiratory mechanics and pulmonary immunity remains largely unknown. Here a systematic study on the interactions between an animal-derived natural PS and aerosols of water and representative mineral and vegetable base oils is performed using a novel biophysical assessing technique called constrained drop surfactometry capable of providing in vitro simulations of normal tidal breathing and physiologically relevant temperature and humidity in the lung. It was found that the mineral oil aerosols can impose strong inhibitions to the biophysical property of PS film, while the airborne vegetable oils and water show negligible adverse effects within the studied concentration range. The inhibitory effect is originated from the strong hydrophobicity of mineral oil, which makes it able to disrupt the interfacial molecular ordering of both phospholipid and protein compositions and consequently suppress the formation of condensed phase and multilayer scaffolds in a PS film. ENVIRONMENTAL IMPLICATION: Understanding the biophysical influence of airborne lubricating base oils on pulmonary surfactant (PS) films can provide new insights into the environmental impacts and health concerns of various industrial lubricant products. Here a comparative study on interactions between an animal-derived natural PS film and the aerosols of water and representative mineral and vegetable base oils under the true physiological conditions was conducted in situ using constrained drop surfactometry. We show that the most frequently used mineral base oil can cause strong inhibitions to the PS film by disrupting the molecular ordering of saturated phospholipids and surfactant-associated proteins at the interface.

Versatile MXene Gels Assisted by Brief and Low-Strength Centrifugation.

Due to the mutual repulsion between their hydrophilic surface terminations and the high surface energy facilitating their random restacking, 2D MXene nanosheets usually cannot self-assemble into 3D macroscopic gels with various applications in the absence of proper linking agents. In this work, a rapid spontaneous gelation of Ti3C2Tx MXene with a very low dispersion concentration of 0.5 mg mL-1 into multifunctional architectures under moderate centrifugation is illustrated. The as-prepared MXene gels exhibit reconfigurable internal structures and tunable rheological, tribological, electrochemical, infrared-emissive and photothermal-conversion properties based on the pH-induced changes in the surface chemistry of Ti3C2Tx nanosheets. By adopting a gel with optimized pH value, high lubrication, exceptional specific capacitances (~ 635 and ~ 408 F g-1 at 5 and 100 mV s-1, respectively), long-term capacitance retention (~ 96.7% after 10,000 cycles) and high-precision screen- or extrusion-printing into different high-resolution anticounterfeiting patterns can be achieved, thus displaying extensive potential applications in the fields of semi-solid lubrication, controllable devices, supercapacitors, information encryption and infrared camouflaging.

Polydopamine-PEG-Folic Acid Conjugate Film Engineered TiO2 Nanotube Arrays for Photoelectrochemical Sensing of Folate Binding Protein.

Serum-soluble folate binding protein (FBP) is an important tumor marker, and the development of a simple biosensing method is highly needed. In this work, a photoelectrochemical (PEC) biosensor for the detection of FBP was proposed based on the construction of an antifouling interface and the unique ligand-protein recognition. The PEC sensing platform was prepared by the biomimetic polydopamine (PDA) coating on TiO2 nanotubes arrays (NTAs). A significant PEC enhancement effect was obtained due to the macroporous structures. Excellent antifouling performance was achieved by conjugation of amino-group-terminated 8-arm poly(ethylene glycol) (PEG). The incorporation of folic acid (FA) retains the antifouling property and shows recognition abilities toward FBP. The fabricated PEC biosensor shows good analytical performance. The combination of ligand-protein recognition and a PEC antifouling interface provides a good consideration for the development of FBP biosensors.

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears.

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.

The predictive value of p16(INK4a) and hybrid capture 2 human papillomavirus testing for high-grade cervical intraepithelial neoplasia.

We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women with LSIL compared with 97.1% of women with HSIL. In contrast, HC2 testing was positive in 85.0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for16(INK4a) between LSIL and HSIL was significant (P < .001), whereas, for HC2, it was not (P = .264). In patients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33.3%) was significantly higher than the PPV of HC2 results (21.2%) (P < .001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.

Expression of HPV16 E5 produces enlarged nuclei and polyploidy through endoreplication.

Anogenital cancers and head and neck cancers are causally associated with infection by high-risk human papillomavirus (HPV). The mechanism by which high-risk HPVs contribute to oncogenesis is poorly understood. HPV16 encodes three genes (HPV16 E5, E6, and E7) that can transform cells when expressed independently. HPV16 E6 and E7 have well-described roles causing genomic instability and unregulated cell cycle progression. The role of HPV16 E5 in cell transformation remains to be elucidated. Expression of HPV16 E5 results in enlarged, polyploid nuclei that are dependent on the level and duration of HPV16 E5 expression. Live cell imaging data indicate that these changes do not arise from cell-cell fusion or failed cytokinesis. The increase in nuclear size is a continual process that requires DNA synthesis. We conclude that HPV16 E5 produces polyploid cells by endoreplication. These findings provide insight into how HPV16 E5 can contribute to cell transformation.

Characterization of the plasma membrane localization and orientation of HPV16 E5 for cell-cell fusion.

Human papillomavirus (HPV) is a non-enveloped DNA virus with an approximately 8000 base pair genome. Infection with certain types of HPV is associated with cervical cancer, although the molecular mechanism by which HPV induces carcinogenesis is poorly understood. Three genes encoded by HPV16 are regarded as oncogenic - E5, E6, and E7. The role of E5 has been controversial. Expression of HPV16 E5 causes cell-cell fusion, an event that can lead to increased chromosomal instability, particularly in the presence of cell cycle checkpoint inhibitors like HPV16 E6 and E7. Using biochemical and cell biological assays to better understand HPV16 E5, we find that HPV16 E5 localizes to the plasma membrane with an intracellular amino terminus and an extracellular carboxyl-terminus. Further, HPV16 E5 must be expressed on both cells for cell fusion to occur. When the extracellular epitope of HPV16 E5 is targeted with an antibody, the number of bi-nucleated cells decreases.

Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion.

Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes--E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis.

A non-invasive technique for quantifying and isolating fused cells.

Cell-cell fusion is an important biological and pathological event. There are limited techniques for studying both the process of cell-cell fusion and the fate of fused cells. We have developed a non-invasive assay for the temporal analysis of cell-cell fusion, quantification of fused cells, and isolation of fused cells. Briefly, cells are transfected with either the T7 bacteriophage RNA polymerase, or yellow fluorescent protein (YFP) driven by a T7 specific promoter. Cells are mixed and induced to fuse. When cells expressing T7 RNA polymerase and T7 promoter driven YFP (T7-YFP) fuse and the cellular contents mix, the YFP is expressed. These YFP-positive cells can be detected with a fluorescent microscope, quantified by flow cytometry, or collected using fluorescence associated cell sorting. Isolated YFP-positive cells can be monitored to determine the fate of fused cells, specifically for the rates of growth, transformation, and changes in chromosome number.

Human papillomavirus genotyping and p16INK4a expression in cervical intraepithelial neoplasia of adolescents.

Adolescents have high rates of human papillomavirus (HPV) infection, and persistent high-risk HPV infection can lead to the development of cervical cancer. The cyclin-dependent kinase inhibitor, p16(INK4a) is overexpressed in cervical intraepithelial neoplasia (CIN), probably due to a persistent and integrated HPV infection. This study investigated p16(INK4a) expression, grades of CIN, and high-risk HPV infection in adolescent cervical biopsies. Biopsies were immunohistochemically stained for p16(INK4a). The presence of wide-spectrum, low-risk, or high-risk HPV was determined by amplifying DNA extracted from the cervical biopsies. Biopsies were classified as cervicitis, 15 cases; CIN 1, 48 cases; CIN 2, 46 cases, and CIN 3, 52 cases. The distribution of p16(INK4a) staining was graded as patchy, diffuse basal, and diffuse full thickness. Pearson's chi(2) tests analyzed the relationships between p16(INK4a) staining, HPV infection, and CIN. Biopsies of cervicitis were negative for HPV and for p16(INK4a) expression. High-risk HPV 16, 18, and 31 increased from 18% in CIN 1 to 66% in CIN 2/3 (P<0.001). In CIN 1, p16(INK4a) was positive in 44% of biopsies with 35% showing patchy, 7% diffuse basal, and one case (2%) showing diffuse full thickness staining. In CIN 2/3, p16(INK4a) was positive in 97% of biopsies with 23% showing patchy, 21% diffuse basal, and 53% diffuse full thickness staining. The difference in the proportions of biopsies showing patchy p16(INK4a) staining in CIN 1 and diffuse full thickness staining in CIN 2/3 was significant (P<0.001). In CIN 1, 61% of high-risk HPV-positive biopsies were p16(INK4a) negative, while all high-risk HPV-positive CIN 2/3 biopsies were p16(INK4a) positive. Diffuse, full thickness p16(INK4a) expression discriminated low-grade from high-grade CIN and appears to be a marker of persistent high-risk HPV infection.