Novel characteristics of soluble fibrin: hypercoagulability and acceleration of blood sedimentation rate mediated by its generation of erythrocyte-linked fibers.

Soluble fibrin (SF) in blood consists of monomers lacking both fibrinopeptides A with a minor population in multimeric clusters. It is a substantial component of isolated fibrinogen (fg), which spontaneously self-assembles into protofibrils progressing to fibers at sub-physiologic temperatures, a process enhanced by adsorption to hydrophobic and some metal surfaces. Comparisons of SF-rich (FR) and SF-depleted (FD) fg isolates disclosed distinct molecular imprints of each via an adsorption/desorption procedure using gold surfaced silica microplates. Accelerated plasminogen activator-induced lysis and decreased stiffness (G') of thrombin-induced FR fg clots were revealed by thomboelastography. Erythrocyte sedimentation (ESR) in afibrinogenemic plasma (Hematocrit 25-33%) was accelerated by FR fg nearly threefold that of FD fg. Stained smears disclosed frequent rouleaux formations and fibers linking stacked erythrocytes in contrast to no rouleaux by FD fg. Rouleaux formations were more pronounced at 4 °C than at ambient temperatures and at fiber-membrane contacts displayed irregular, knobby membrane contours. One of several FR fg isolates also displayed incomplete fiber networks in cell-free areas. What is more, pre-mixing FR fg with each of three monoclonal IgG anti-fg antibodies at 1.5 mol/mol fg, that inhibited fibrin polymerization, prevented rouleaux formation save occasional 2-4 erythrocyte aggregates. We conclude that spontaneously generated SF fibers bound to erythrocytes forming intercellular links culminating in rouleaux formation and ensuing ESR acceleration which in clinical settings reflects hypercoagulability. Also, the results can explain the reported fg binding to erythrocytes via ligands such as CD47, stable in vivo RBC aggregates in capillaries, and red areas of pathologic thrombi.

Stretchable and Self-Healable Poly(styrene-co-acrylonitrile) Elastomer with Metal-Ligand Coordination Complexes.

Recently, soft electronics have attracted significant attention for various applications such as flexible devices, artificial electronic skins, and wearable devices. For practical applications, the key requirements are an appropriate electrical conductivity and excellent elastic properties. Herein, using the cyano-silver complexes resulting from coordination bonds between the nitrile group of poly(styrene-co-acrylonitrile) (SAN) and Ag ions, a self-healing elastomer demonstrating electrical conductivity is obtained. Because of these coordination complexes, the Ag-SAN elastomer possesses elasticity, compared with pristine SAN. The fracture strain of the Ag-SAN elastomers increased with the amount of added Ag ions, reaching up to 1000%. Additionally, owing to the presence of reversible coordination bonds, the elastomer exhibits self-healing properties at room temperature and electrical conductivity, thereby improving the possibility of its utilization in novel applications wherein elastic materials are generally exposed to external stimuli.

Dewetting of Thin Polymer Films on Wrinkled Graphene Oxide Monolayers.

We investigated the effect of the morphological structure of a graphene oxide (GO) monolayer on the dewetting dynamics of the upper polymer thin films. The Langmuir-Schaefer (LS) technique was used to prepare a wrinkled GO ( wrGO) structure with a root mean square (rms) roughness of 22.7 Å. The dewetting behavior of poly(methyl methacrylate) (PMMA) thin films on the wrGO monolayers was perfectly prevented, whereas the PMMA thin films on a flat GO monolayer were dewetted at 203 °C. This wrinkle effect of the GO can be also obtained when the GOs monolayers are intercalated to the PMMA/polystyrene (PS) interface. In this multilayer, the flat GO monolayer at the interface between the PS and PMMA layers was spontaneously roughened with rms roughness of 46.9 Å after annealing and also prohibited the dewetting behavior. From the results, we found that to improve the compatibility of polymer blends by adding the two-dimensional nanosheets, it is important to control the morphological structure of the sheets at the interface, along with manipulation of the GO-polymer interactions.

Perpendicular Orientation of Diblock Copolymers Induced by Confinement between Graphene Oxide Sheets.

We have studied an orientation structure of self-assembled block copolymers (dPS-b-PMMA) of deuterated polystyrene (dPS) and poly(methyl methacrylate) (PMMA) confined between graphene oxide (GO) surfaces. The results of combination techniques, such as neutron reflectivity, time-of-flight secondary-ion mass spectrometry, grazing-incidence small-angle X-ray scattering, and scanning electron microscopy, show that self-assembled domains of the block copolymers in thin films near the GO sheets are oriented perpendicular to the surface of the GO monolayers, in contrast to the horizontal lamellar structure of the copolymer thin film in the absence of the GO monolayers. This is due to the amphiphilic nature of the GO, which leads to a nonpreferential interaction of both dPS and PMMA blocks. Double-sided confinement with the GO monolayers further extends the ordering behavior of the dPS-b-PMMA thin films. Continuous vertical orientation of the block copolymer thin films is also obtained in the presence of alternating GO layers within thick copolymer films.

Graphene Oxide Monolayer as a Compatibilizer at the Polymer-Polymer Interface for Stabilizing Polymer Bilayer Films against Dewetting.

We investigate the effect of adding graphene oxide (GO) sheets at the polymer-polymer interface on the dewetting dynamics and compatibility of immiscible polymer bilayer films. GO monolayers are deposited at the poly(methyl methacrylate) (PMMA)-polystyrene (PS) interface by the Langmuir-Schaefer technique. GO monolayers are found to significantly inhibit the dewetting behavior of both PMMA films (on PS substrates) and PS films (on PMMA substrates). This can be interpreted in terms of an interfacial interaction between the GO sheets and these polymers, which is evidenced by the reduced contact angle of the dewet droplets. The favorable interaction of GO with both PS and PMMA facilitates compatibilization of the immiscible polymer bilayer films, thereby stabilizing their bilayer films against dewetting. This compatibilization effect is verified by neutron reflectivity measurements, which reveal that the addition of GO monolayers broadens the interface between PS and the deuterated PMMA films by 2.2 times over that of the bilayer in the absence of GO.

Morphology control of surfactant-assisted graphene oxide films at the liquid-gas interface.

Control of a two-dimensional (2D) structure of assembled graphene oxide (GO) sheets is highly desirable for fundamental research and potential applications of graphene devices. We show that an alkylamine surfactant, i.e., octadecylamine (ODA), Langmuir monolayer can be utilized as a template for adsorbing highly hydrophilic GO sheets in an aqueous subphase at the liquid-gas interface. The densely packed 2-D monolayer of such complex films was obtained on arbitrary substrates by applying Langmuir-Schaefer or Langmuir-Blodgett technique. Morphology control of GO sheets was also achieved upon compression by tuning the amount of spread ODA molecules. We found that ODA surfactant monolayers prevent GO sheets from sliding, resulting in formation of wrinkling rather than overlapping at the liquid-gas interface during the compression. The morphology structures did not change after a graphitization procedure of chemical hydrazine reduction and thermal annealing treatments. Since morphologies of graphene films are closely correlated to the performance of graphene-based materials, the technique employed in this study can provide a route for applications requiring wrinkled graphenes, ranging from nanoelectronic devices to energy storage materials, such as supercapacitors and fuel cell electrodes.

Embedded Direct Ink Writing 3D Printing of UV Curable Resin/Sepiolite Composites with Nano Orientation.

Among the various 3D printing methods, direct ink writing (DIW) through extrusion directly affects the microstructure and properties of materials. However, use of nanoparticles at high concentrations is restricted due to difficulties in sufficient dispersion and the deteriorated physical properties of nanocomposites. Thus, although there are many studies on filler alignment with high-viscosity materials with a weight fraction higher than 20 wt %, not much research has been done with low-viscosity nanocomposites with less than 5 phr. Interestingly, the alignment of anisotropic particles improves the physical properties of the nanocomposite at a low concentration of nanoparticles with DIW. The rheological behavior of ink is affected by the alignment of anisotropic sepiolite (SEP) at a low concentration using the embedded 3D printing method, and silicone oil complexed with fumed silica is used as a printing matrix. A significant increase in mechanical properties is expected compared to conventional digital light processing. We clarify the synergistic effect of the SEP alignment in a photocurable nanocomposite material through physical property investigations.

Acentric 2-D ensembles of D-br-A electron-transfer chromophores via vectorial orientation within amphiphilic n-helix bundle peptides for photovoltaic device applications.

We show that simply designed amphiphilic 4-helix bundle peptides can be utilized to vectorially orient a linearly extended donor-bridge-acceptor (D-br-A) electron transfer (ET) chromophore within its core. The bundle's interior is shown to provide a unique solvation environment for the D-br-A assembly not accessible in conventional solvents and thereby control the magnitudes of both light-induced ET and thermal charge recombination rate constants. The amphiphilicity of the bundle's exterior was employed to vectorially orient the peptide-chromophore complex at a liquid-gas interface, and its ends were tailored for subsequent covalent attachment to an inorganic surface, via a "directed assembly" approach. Structural data, combined with evaluation of the excited state dynamics exhibited by these peptide-chromophore complexes, demonstrate that densely packed, acentrically ordered 2-D monolayer ensembles of such complexes at high in-plane chromophore densities approaching 1/200 Å(2) offer unique potential as active layers in binary heterojunction photovoltaic devices.

Control of anti-thrombogenic properties: surface-induced self-assembly of fibrinogen fibers.

Wound healing is a complex process initiated by the formation of fibrin fibers and endothelialization. Normally, this process is triggered in a wound by thrombin cleavage of fibrinopeptides on fibrinogen molecules, which allows them to self spontaneously-assemble into large fibers that provide the support structure of the clot and promote healing. We have found that the fibrous structures can also form without thrombin on most polymer or metal surfaces, including those commonly used for stents. We show that the relatively hydrophobic E and D regions of the fibrinogen molecule are adsorbed on these surfaces, exposing the αC domains, which in turn results in the formation of large fiber structures that promote endothelial cell adhesion. We show that the entire process can be suppressed when stents or other substrates are coated with polymers that are functionalized to bind the αC domains, leading to the development of potentially nonthrombogenic implant materials.

Multifunctional and thermoresponsive methylcellulose composite hydrogels with photothermal effect.

Multifunctional and thermoresponsive hydrogels can be used as soft materials in various medical applications, such as beauty devices, drug delivery, and near-infrared (NIR) lasers. In this study, methylcellulose (MC) composite hydrogels containing tannic acid (TA) and Fe3+ were prepared via a simple, fast process. The MC composite hydrogel contains hydrogen bonds between the MC polymer and TA and coordination bonds between TA and Fe3+, without losing the reversible thermogelation properties of the MC polymer. The gelation rates and mechanical properties of the MC composite hydrogel were controlled by varying its TA and Fe3+ contents. In particular, the hydrogel with a TA-Fe chelating complex showed an excellent photothermal effect, indicating its potential application in cosmetic beauty devices. It also exhibited UV-blocking, antioxidant, and antibacterial properties owing to the multifunctional TA. The facile processing of these MC/TA/Fe hydrogels provides new opportunities for biomedical applications and beauty devices employing NIR laser therapy.

Factors influencing the outcome of breast cancer patients with 10 or more metastasized axillary lymph nodes.

BACKGROUND: The purpose of this study was to investigate prognostic factors in breast cancer patients with metastasis of ten or more lymph nodes (pathologic N3a). METHODS: We conducted a retrospective analysis of the cases of 304 breast cancer patients with pathologic N3a disease who had undergone definitive surgery between 1986 and 2006, and investigated the correlation between clinicopathologic characteristics and treatment outcomes. RESULTS: With a median follow-up period of 55 months, the 5-year disease-free survival rate was 42.9% and the overall survival rate was 57.8%. Univariate analysis showed that the factors associated with poor disease-free survival were: age < 35 years (P = 0.001), history of neoadjuvant chemotherapy (P < 0.001), T4 stage (P < 0.001), 20 or more positive lymph nodes (P < 0.001), presence of lymphovascular invasion (P = 0.003), and negative progesterone receptor expression (P = 0.003). Multivariate analysis showed the factors with independent prognostic significance to be: history of neoadjuvant chemotherapy (hazard ratio [HR] 3.163; 95% confidence interval [CI], 2.025-4.941; P < 0.001), 20 or more positive nodes (HR 1.598; 95% CI, 1.063-2.402; P = 0.024), and presence of lymphovascular invasion (HR 1.636; 95% CI, 1.009-2.654; P = 0.046). Factors associated with poor overall survival in univariate analysis were: age < 35 years (P = 0.033), history of neoadjuvant chemotherapy (P < 0.001), T4 stage (P = 0.001), 20 or more positive lymph nodes (P < 0.001), and negative progesterone receptor expression (P = 0.013). Multivariate analysis showed these factors to be: history of neoadjuvant chemotherapy (HR 2.900; 95% CI, 2.011-4.182; P < 0.001), and 20 or more positive nodes (HR 1.956; 95% CI, 1.419-2.696; P < 0.001). CONCLUSION: Cases of breast tumors with extensive nodal metastasis were found to be heterogeneous in terms of prognosis. History of previous neoadjuvant chemotherapy and higher numbers of metastatic lymph nodes were found to be the two most important prognostic markers for pathologic N3a disease. New strategies such as biologic therapy and novel combinations should be considered for application in patients with poor prognosis, rather than conventional treatment.

Efficacy of Immunohistochemistry for SDHB in the Screening of Hereditary Pheochromocytoma-Paraganglioma.

The most common genetic backgrounds of hereditary paraganglioma and pheochromocytoma (PPGL) are SDHx germline mutations. Given the fact that the immunohistochemistry (IHC) result for SDHB is always negative regardless of the type of SDHx mutation, we aimed to evaluate the efficacy of using SDHB IHC for screening SDHx mutations in PPGL cases. In total, 52 patients who underwent surgery for PPGL treatment between 2006 and 2020 and underwent genetic analysis at diagnosis were included. Tissue microarrays (TMAs) were constructed with PPGL tissues and IHC for SDHB was performed on TMA sections. All 10 patients with SDHB-negative IHC contained SDHB or SDHD mutations. The genetic test results of patients with SDHB-weakly positive IHC varied (one SDHB, two RET, one VHL, and three unknown gene mutations). There were no SDHx mutations in the SDHB-positive IHC group. Six patients with weakly positive SDHB IHC with primarily unknown genetic status were re-called and underwent next-generation sequencing. None of them had SDHx mutations. In conclusion, SDHB-negative IHC is a cost-effective and reliable method to predict SDHx mutations. However, in the case of weakly positive SDHB staining, an additional gene study should be considered.

Fibers Generated by Plasma Des-AA Fibrin Monomers and Protofibril/Fibrinogen Clusters Bind Platelets: Clinical and Nonclinical Implications.

Objective Soluble fibrin (SF) is a substantial component of plasma fibrinogen (fg), but its composition, functions, and clinical relevance remain unclear. The study aimed to evaluate the molecular composition and procoagulant function(s) of SF. Materials and Methods Cryoprecipitable, SF-rich (FR) and cryosoluble, SF-depleted (FD) fg isolates were prepared and adsorbed on one hydrophilic and two hydrophobic surfaces and scanned by atomic force microscopy (AFM). Standard procedures were used for fibrin polymerization, crosslinking by factor XIII, electrophoresis, and platelet adhesion. Results Relative to FD fg, thrombin-induced polymerization of FR fg was accelerated and that induced by reptilase was markedly delayed, attributable to its decreased (fibrinopeptide A) FpA. FR fg adsorption to each surface yielded polymeric clusters and co-cryoprecipitable solitary monomers. Cluster components were crosslinked by factor XIII and comprised ≤21% of FR fg. In contrast to FD fg, FR fg adsorption on hydrophobic surfaces resulted in fiber generation enabled by both clusters and solitary monomers. This began with numerous short protofibrils, which following prolonged adsorption increased in number and length and culminated in surface-linked three-dimensional fiber networks that bound platelets. Conclusion The abundance of adsorbed protofibrils resulted from (1) protofibril/fg clusters whose fg was dissociated during adsorption, and (2) adsorbed des-AA monomers that attracted solution counterparts initiating protofibril assembly and elongation by their continued incorporation. The substantial presence of both components in transfused plasma and cryoprecipitate augments hemostasis by accelerating thrombin-induced fibrin polymerization and by tightly anchoring the resulting clot to the underlying wound or to other abnormal vascular surfaces.

Janus Graphene Oxide Sheets with Fe3O4 Nanoparticles and Polydopamine as Anodes for Lithium-Ion Batteries.

In this study, a one-step process to fabricate "Janus"-structured nanocomposites with iron oxide (Fe3O4) nanoparticles (Fe3O4 NPs) and polydopamine (PDA) on each side of a graphene oxide (GO) nanosheet using the Langmuir-Schaefer technique has been proposed. The Fe3O4 NPs-GO hybrid is used as a high-capacity active material, while PDA is added as a binder due to its unique wet-resistant adhesive property. The transmission electron microscopy image shows a superlattice-like out-of-plane section of the multilayered nanocomposite, which maximizes the density of the composite materials. Grazing-incidence small-angle X-ray scattering results combined with scanning electron microscopy images confirm that the multilayered Janus composite exhibits an in-plane hexagonal array structure of closely packed Fe3O4 NPs. This Janus multilayered structure is expected to maximize the amount of active material in a specific volume and reduce volume changes caused by the conversion reaction of Fe3O4 NPs. According to the electrochemical results, the Janus multilayer electrode delivers an excellent capacity of ∼903 mAh g-1 at a current density of 200 mA g-1 and a reversible capacity of ∼639 mAh g-1 at 1 A g-1 up to the 1800th cycle, indicating that this Janus composite can be a promising anode for Li-ion batteries.

Clinicopathological characteristics of mucinous carcinoma of the breast in Korea: comparison with invasive ductal carcinoma-not otherwise specified.

Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.

Large-Area 2D-MXene Nanosheet Assemblies Using Langmuir-Schaefer Technique: Wrinkle formation.

The formation of uniform sheets of exfoliated MXene over a large area is important for improving their performance in practical applications. In this study, the Langmuir-Schaefer technique was employed to deposit uniform MXene sheets on a solid substrate and control the morphological structure over a large area. At the liquid-gas interface, MXene flakes were densely compressed into nanosheets with minimal gaps between them at 20 mN/m. Through further compression, the wrinkle morphologies of MXene sheets tend to be perpendicularly aligned to the compression direction. These wrinkle structures were also exhibited when MXene sheets were mixed in equal proportions with graphene oxide sheets. Owing to the close correlation of the morphologies of MXene films with the performance of MXene-based materials, the technique employed in this study can provide a route for applications requiring wrinkled MXene, ranging from nanoelectronic devices to energy storage materials, such as supercapacitors and battery electrodes.

Position-Dependent Diffusion Dynamics of Entangled Polymer Melts Nanoconfined by Parallel Immiscible Polymer Films.

The morphological structure and dynamics of confined polymers adjacent to the polymer-polymer interface have a profound effect on determining the overall physical properties of polymer blends. We measured the diffusion dynamics of poly(methyl methacrylate) (PMMA) melts confined between polystyrene (PS) layers using neutron reflectivity. Combinations of various thicknesses of PMMA and deuterated PMMA (dPMMA) allowed us to experimentally reveal the nonmonotonic behavior of polymer mobility near the PS-PMMA interface. From the neutron reflectivity results, we found that the polymers adjacent to the immiscible polymer-polymer interface showed enhanced diffusion dynamics because of the repulsive interaction between PS and PMMA, whereas the polymer at local regions farther from the interface exhibited reduced dynamics. This is probably due to the nonspherical conformation of PMMA and spatial confinement near the PS-PMMA interface.

Instantaneous integration of magnetite nanoparticles on graphene oxide assisted by ultrasound for efficient heavy metal ion retrieval.

We fabricated a magnetite nanoparticle-graphene oxide (GO) hybrid via a non-chemical and one-step process assisted by ultrasound in an aqueous solution where the nanoparticle attached to the hydrophobic region on graphite oxide (multi-layered GO) which, at the same time, was exfoliated. Unlike chemical methods such as precipitation, oxygen-containing functional groups on GO have not been consumed or reduced during the hybridization, leading that this hybrid exhibited good water solubility and high adsorption capacity for heavy metal ions such as Pb(II) and Au(III). After the adsorption, the hybrid was instantly collected using a magnet. This method can be useful for hybridizing various nanoparticles with GO.

3D Printing of Polyethylene Terephthalate Glycol-Sepiolite Composites with Nanoscale Orientation.

A fused-deposition modeling (FDM) 3D-printed polyethylene terephthalate glycol (PETG)-sepiolite composite showed effective synergetic mechanical reinforcement in tensile testing compared to an injection-molded composite. The results showed that the addition of 3 phr sepiolite improved the tensile strength of 3D-printed PETG samples by 35.4%, while the tensile strength of injection-molded PETG samples was improved by 7.2%. To confirm these phenomena, FDM PETG-sepiolite composites were investigated by small-angle X-ray scattering to correlate the nanostructures of the composites with their mechanical strengths. The small-angle X-ray scattering data and transmission electron microscopy observations demonstrated that needle-shaped sepiolite particles were aligned in the printing direction. This fine oriented nanostructure formed during 3D printing created a synergistic effect that improved the material properties of the composite. These novel PETG-sepiolite composites with enhanced mechanical properties can be promising materials fabricated via FDM 3D printing.