The photoluminescence signals of a graphene/MoS2 heterostructural stacking film are sensitive to environmental charges, which allows the single‐base sequence‐selective detection of DNA hybridization ...with sensitivity to the level of aM.
There is broad interest in using graphene or graphene oxide sheets as a transducer for label‐free and selective electrical detection of biomolecules such as DNA. However, it is still not well ...explored how the DNA molecules interact with and influence the properties of graphene during the detection. Here, Hall effect measurements based on the Van der Pauw method are used to perform single‐base sequence selective detection of DNA on graphene sheets, which are prepared by chemical vapor deposition. The sheet resistance increases and the mobility decreases with the addition of either complementary or one‐base mismatched DNA to the graphene device. The hole carrier concentration of the graphene devices increases significantly with the addition of complementary DNA but it is less affected by the one‐base mismatched DNA. It is concluded that the increase in hole carrier density, indicating p‐doping to graphene, is better correlated with the DNA hybridization compared to the commonly used parameters such as conductivity change. The different electrical observations of p‐doping from Hall effect measurements and n‐doping from electrolyte‐gated transistors can be explained by the characteristic morphology of partially hybridized DNA on graphene and the mismatch between DNA chain length and Debye length in electrolytes.
Label‐free, single‐base sequence selective detection of DNA hybridization based on a single‐layer graphene device is investigated using Hall effect measurements with the Van der Pauw method. The increase in hole carrier density, indicating p‐doping to graphene, is better correlated to the DNA hybridization compared with the commonly used parameters such as conductivity change.
Focal adhesions undergo myosin-II-mediated maturation wherein they grow and change composition to modulate integrin signalling for cell migration, growth and differentiation. To determine how focal ...adhesion composition is affected by myosin II activity, we performed proteomic analysis of isolated focal adhesions and compared protein abundance in focal adhesions from cells with and without myosin II inhibition. We identified 905 focal adhesion proteins, 459 of which changed in abundance with myosin II inhibition, defining the myosin-II-responsive focal adhesion proteome. The abundance of 73% of the proteins in the myosin-II-responsive focal adhesion proteome was enhanced by contractility, including proteins involved in Rho-mediated focal adhesion maturation and endocytosis- and calpain-dependent focal adhesion disassembly. During myosin II inhibition, 27% of proteins in the myosin-II-responsive focal adhesion proteome, including proteins involved in Rac-mediated lamellipodial protrusion, were enriched in focal adhesions, establishing that focal adhesion protein recruitment is also negatively regulated by contractility. We focused on the Rac guanine nucleotide exchange factor β-Pix, documenting its role in the negative regulation of focal adhesion maturation and the promotion of lamellipodial protrusion and focal adhesion turnover to drive cell migration.
Directed cell migration is an important step in effective wound healing and requires the dynamic control of the formation of cell-extracellular matrix interactions. Plasma fibronectin is an ...extracellular matrix glycoprotein present in blood plasma that plays crucial roles in modulating cellular adhesion and migration and thereby helping to mediate all steps of wound healing. In order to seek safe sources of plasma fibronectin for its practical use in wound dressing, we isolated fibronectin from human (homo) and porcine plasma and demonstrated that both have a similar ability as a suitable substrate for the stimulation of cell adhesion and for directing cell migration. In addition, we also defined the N-glycosylation sites and N-glycans present on homo and porcine plasma fibronectin. These N-glycosylation modifications of the plasma fibronectin synergistically support the integrin-mediated signals to bring about mediating cellular adhesion and directed cell migration. This study not only determines the important function of N-glycans in both homo and porcine plasma fibronectin-mediated cell adhesion and directed cell migration, but also reveals the potential applications of porcine plasma fibronectin if it was applied as a material for clinical wound healing and tissue repair.
Sulfated glycans are known to be involved in several glycan-mediated cell adhesion and recognition pathways. Our mRNA transcript analyses on the genes involved in synthesizing GlcNAc-6-O–sulfated ...glycans in human colon cancer tissues indicated that GlcNAc6ST-2 (CHST4) is preferentially expressed in cancer cells compared with nonmalignant epithelial cells among the three known major GlcNAc-6-O-sulfotransferases. On the contrary, GlcNAc6ST-3 (CHST5) was only expressed in nonmalignant epithelial cells, whereas GlcNAc6ST-1 (CHST2) was expressed equally in both cancerous and nonmalignant epithelial cells. These results suggest that 6-O-sulfated glycans that are synthesized only by GlcNAc6ST-2 may be highly colon cancer–specific, as supported by immunohistochemical staining of cancer cells using the MECA-79 antibody known to be relatively specific to the enzymatic reaction products of GlcNAc6ST-2. By more precise MS-based sulfoglycomic analyses, we sought to further infer the substrate specificities of GlcNAc6STs via a definitive mapping of various sulfo-glycotopes and O-glycan structures expressed in response to overexpression of transfected GlcNAc6STs in the SW480 colon cancer cell line. By detailed MS/MS sequencing, GlcNAc6ST-3 was shown to preferentially add sulfate onto core 2–based O-glycan structures, but it does not act on extended core 1 structures, whereas GlcNAc6ST-1 prefers core 2–based O-glycans to extended core 1 structures. In contrast, GlcNAc6ST-2 could efficiently add sulfate onto both extended core 1– and core 2–based O-glycans, leading to the production of unique sulfated extended core 1 structures such as R-GlcNAc(6-SO3−)β1-3Galβ1–4GlcNAc(6-SO3−)β1–3Galβ1–3GalNAcα, which are good candidates to be targeted as cancer-specific glycans.
Background
This study evaluated the ameliorative effect of hesperidin (HES), an anti‐inflammatory flavanone, in rats with ligation (Lig)‐induced periodontitis.
Methods
A total of 48 rats were ...randomly divided into non‐ligation group (NL), Lig group, and two ligation‐plus‐HES groups (L+H). HES was administered immediately after ligature placement at a dose of 75 or 150 mg/kg by intragastric feeding. Destruction of the ligated maxillary second and mandibular first molars were evaluated by dental radiography, microcomputed tomography (micro‐CT), and histometry performed after sacrificing the rats on the seventh day. The expression levels of interleukin (IL)‐1β, IL‐6, and inducible nitric oxide synthase (iNOS) messenger (m)RNAs in the gingiva were determined by reverse‐transcription polymerase chain reaction. The expression of iNOS was examined by immunohistochemistry.
Results
The dental radiography and micro‐CT findings revealed significantly increased alveolar bone loss in the Lig group, which was significantly prevented by HES. The histometry results revealed less gingival inflammation and connective tissue loss in the L+H groups compared with that in the Lig group. The mRNA expression levels of IL‐6, IL‐1 β, and iNOS were significantly increased in the Lig group but were reduced in the L+H groups. The immunostaining results showed that the ligation‐induced iNOS expression was also decreased by HES.
Conclusions
Oral administration of HES promotes an ameliorative effect against the ligation‐induced alveolar bone loss and effectively inhibits the production of proinflammatory mediators in rats with experimentally induced periodontitis. Therefore, HES may be a good candidate for modulating oral inflammatory diseases.
Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a ...comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and high mannose glycans, complex glycans with 2-4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation profiles were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Compared to CVF from women experiencing term birth, CVF from women who subsequently experienced preterm birth showed lower sialylation, which correlated to the presence of a diverse microbiome, and higher fucosylation, which correlated positively to pro-inflammatory cytokine concentration. This study is the first step towards better understanding the role of cervicovaginal glycans in reproductive health, their contribution to the mechanism of microbial driven preterm birth, and their potential for preventative therapy.
Background:
Hepatectomy is one potential treatment for intrahepatic cholangiocarcinoma (IHCC). Recurrent rate is high after curative resection and most recurrences occur within residual liver ...parenchyma. The aim of this study was to elucidate the impact of different treatment modalities on recurrent diseases in patients with IHCC after primary liver resection.
Methods:
Between February 1999 and December 2015, we retrospectively identified patients who received curative resection for IHCC. Patients who experienced recurrences were included. Locoregional therapies included re-hepatectomy, radiofrequent ablation, and transhepatic arterial chemoembolization. These patients were categorized into three groups: intrahepatic recurrence without locoregional therapies (group A), intrahepatic recurrence with locoregional therapies (group B) and extrahepatic metastases (group C).
Results:
Forty-three patients were included and there were 12, 15, and 16 patients in groups A, B, and C, respectively. The median disease-free survival times were 8.3, 9.1, and 8.7 months in groups A, B, and C (p = 0.099). The median after-recurrence overall survival times (period between recurrence and death/censor) were 6.4, 34.0, and 8.3 months in groups A, B, and C (p = 0.001). Locoregional therapies showed favorable benefit in multivariant analysis (hazard ratio: 0.274, confidence interval: 0.083–0.908, p = 0.010).
Conclusion:
Locoregional therapies offered favorable benefits for patients with recurrent intrahepatic cholangiocarcinoma.
Abstract A graphene-based flexible microprobe developed by microelectromechanical system technology shows high resolution for the detection of electrophysiological signals from various bio-objects. ...The hydrophilization post-treatment using steam plasma was performed on the graphene surface to decrease the interfacial impedance between graphene and electrolyte, and thus improve the signal-to-noise ratio during neural and cardiac recording. The signal-to-noise ratio of the action potentials from axons of a crayfish measured by hydrophilic-modified graphene microprobe (27.8 ± 4.0 dB) is higher than that of untreated device (20.3 ± 3.3 dB). Also, the form of the QRS complex and T wave in the electrocardiogram of the zebrafish heart can be clearly distinguished using the modified device. The total measured noise levels of the overall stability of the system were 4.2 μVrms (hydrophilic graphene) and 7.64 μVrms (hydrophobic graphene). The graphene-based implant can be further used for in vivo, long-term recording and retina prosthesis. From the Clinical Editor In this study a graphene-based flexible microprobe developed using microelectromechanical system technology was demonstrated to enable high resolution detection of electrophysiological signals, including EKG in zebrafish models. Both hydrophilic and hydrophobic graphene were studied, paving the way to potential future clinical applications of this new technology.
Graphene sheets made by chemical vapor deposition are transferred onto a glass nanopipette to form graphene strips. Two strips are connected at the nanopipette tip end to form a transistor channel. ...This graphene‐based transistor can be operated in a liquid‐gating condition, thereby allowing the electrical detection of the pH value of a droplet with submicroliter volume.
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