Micelle-based fluorogenic sensing of trypsin: a sensitive method in pancreatic disease diagnosis.

Protamine-mediated micellar aggregates, featuring an AIE-based fluorescent sensor, facilitate efficient detection of trypsin activity. This method enables the detection of trypsin at exceptionally low concentrations (0.01-0.1 µg mL-1) in urine, demonstrating its potential for early clinical diagnosis of trypsin-related pancreatic diseases.

Effect of Bulky Atom Substitution on Backbone Coplanarity and Electrical Properties of Cyclopentadithiophene-Based Semiconducting Polymers.

The effect of atomic substitution on the optoelectronic properties of a coplanar donor-acceptor (D-A) semiconducting polymer (SPs), prepared using cyclopentadithiophene (CDT) and 2,1,3-benzothiadiazole (BT) moieties, is investigated. By substituting a carbon atom in the BT unit with CF or C-Cl, two random D-A SPs are prepared, and their optoelectronic properties are thoroughly investigated. Density functional theory calculations demonstrate that the fluorinated polymer has a slightly smaller dihedral angle (Ï´ = 0.6°) than the pristine polymer (Ï´ = 1.9°) in its lowest-energy conformation, implying efficient charge transport through the coplanar backbone of the fluorinated polymer. However, the chlorinated polymer shows the lowest energy at a relatively larger dihedral angle (Ï´ = 139°) due to the steric hindrance induced by bulky chlorine atoms in the backbone, thereby leading to thin-film morphology, which is unfavorable for charge transport. Consequently, the fluorinated polymer yields the highest field-effect mobility (µ) of 0.57 cm2 V-1 s-1 , slightly higher than that of the pristine polymer (µ = 0.33 cm2 V-1 s-1 ), and the extended device lifetime of organic field-effect transistors over 12 d without any encapsulation layers. The results of this study provide design guidelines for air-stable D-A SPs.

Clinical Effectiveness of Submucosal Injection with Indigo Carmine Mixed Solution for Colon Endoscopic Mucosal Resection.

BACKGROUND/AIMS: Submucosal injection with indigo carmine mixed solution can improve the delineation of colorectal neoplasia during endoscopic mucosal resection (EMR). Thus, the aim of this study was to evaluate the efficacy of submucosal injection with indigo carmine mixed solution during EMR of colorectal neoplasia. METHODS: This was a prospective, randomized, controlled study of a total of 212 neoplastic colon polyps (5-20 mm) subjected to EMR in a single tertiary university hospital. The patients were randomized into two groups according to whether or not indigo carmine mixed solution was used, and the complete resection rate (CRR) after EMR was evaluated. RESULTS: A total of 212 neoplastic polyps (normal saline group, 115; indigo carmine group, 97) were successfully removed by EMR. There was no significant difference in the CRR (92.8 vs. 89.6%, p = 0.414) or macroscopic delineation (86.0 vs. 93.8%, p = 0.118) between the two groups. In a separate analysis of sessile serrated adenomas/polyps (SSAs/Ps), macroscopic delineation was better in the indigo carmine group than the normal saline group (87.5 vs. 53.8%), albeit not significantly (p = 0.103). In univariate analyses, the CRR was significantly related to polyp location, polyp morphology, macroscopic delineation, and pathologic findings. In a multiple logistic regression analysis, macroscopic delineation (odds ratio (OR), 7.616, p = 0.001) and polyp pathology (OR, 8.621; p < 0.001) were significantly associated with the CRR. CONCLUSIONS: Submucosal injection with indigo carmine mixed solution did not improve the CRR or macroscopic delineation of EMR of colorectal neoplasias.

A triple approach for diagnostic assessment of endoscopic ultrasound-guided fine needle aspiration in pancreatic solid masses and lymph nodes.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has been becoming the standard tool for acquiring pancreatic lesion tissue. However, a single cytologic or histologic evaluation is not satisfactory for diagnosis. In this study, we evaluated the diagnostic yield of EUS-FNA for pancreatic solid masses and intra-abdominal lymph nodes using a triple approach. METHODS: This study included patients undergoing evaluation for a solid pancreatic mass (n = 59) or intra-abdominal lymph nodes (n = 16) using EUS-FNA with a 22- or 25-gauge (G) needle, respectively. The specimens from each pass were analyzed by on-site cytology using Diff-Quick stain, cytology using Papanicolaou stain, and histology with immunohistochemical (IHC) staining. RESULTS: A total of 75 patients (49 males; mean age; 63.7 years) were included. The median number of needle pass for diagnosis of malignancy was 2.0, and there was no technical failure. The diagnostic accuracies with on-site cytology, cytology using Papanicolaou staining, and histology were 70.7, 80.0, and 80.0 %, respectively. The diagnostic accuracy using a triple approach was significantly greater than cytology using Papanicolaou staining alone (94.7 vs. 80.0 %; p = 0.007). In patients with malignant lesions, cytology identified 12 of 71 (16.9 %) malignant lesions that were not diagnosed by histology using IHC, and histology identified six (8.5 %) malignant lesions that were not diagnosed by cytology. CONCLUSION: On-site cytopathologic evaluation combined with cytologic and histologic analysis with IHC stain for one-pass specimen is considered to be able to increase the overall accuracy of EUS-FNA in pancreatic solid masses and lymph nodes.

Fluorogenic Monitoring of α-Amylase in Human Urine for Straightforward Diagnosis of Pancreatic Diseases.

In this study, we developed a sensitive method for monitoring α-amylase using a fluorogenic approach based on the host-guest complexation between an amphiphilic pyrenyl derivative (1) and γ-cyclodextrins (γ-CDs). The compound 1 self-assembles into nanofibrils in aqueous solutions. Upon the introduction of γ-CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2 : 2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α-amylase, γ-CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α-amylase in human urine, offering a practical approach for early screening of pancreatic-related diseases.

Synthesis mechanism from graphene quantum dots to carbon nanotubes by ion-sputtering assisted chemical vapor deposition.

We present the first work of the synthesis mechanism from graphene quantum dots (GQDs) to carbon nanotubes (CNTs) by an ion-sputtering assisted chemical vapor deposition. During the annealing process, a Pt thin film deposited by the ion-sputtering was dewetted and agglomerated to form many nanometer-sized particles, leading to Pt nanoparticles (PtNPs) that can act as catalysts for creating carbon allotropes. The shape of the allotropes can be effectively tailored from GQDs to CNTs by controlling three key parameters such as the dose of catalytic ions (D), amounts of carbon source (S), and thermal energy (T). In our work, it was clearly proved that the growth control from GQDs to CNTs has a comparably proportional relationship with D and S, but has a reverse proportional relationship with T. Furthermore, high-purity GQDs without any other by-products and the CNTs with the cap of PtNPs were generated. Their shapes were appropriately controlled, respectively, based on the established synthesis mechanism.

A sensitive and selective mercury(II) sensor based on amplified fluorescence quenching in a conjugated polyelectrolyte/spiro-cyclic rhodamine system.

A novel fluorescence-based sensor for mercury(II) ion is described consisting of a water-soluble, anionic-conjugated polyelectrolyte (CPE) and spiro-cyclic rhodamine derivative (1). A solution containing the CPE (0.1 × 10(-6) M repeat unit concentration) and 1 (1 × 10(-6) M concentration) in aqueous solution exhibits a sensitive and selective turn-off fluorescence response to Hg(II). The Stern-Volmer quenching constant for quenching of the fluorescence of the system by Hg(II) is ≈1.5 × 10(7) M(-1) , and Hg(II) can be sensed with a detection limit <10 × 10(-9) M. A mechanism for the sensor response is proposed and it consists of efficient and selective complex formation between 1 and Hg(II), along with a very high association between the 1-Hg(II) complex and the anionic CPE.

Ultrasensitive Determination of Trypsin in Human Urine Based on Amplified Fluorescence Response.

The determination of trypsin activity in human urine is important for evaluating pancreatic disease. We designed an effective fluorescence sensing strategy based on a self-assembled amphiphilic pyrene/protamine complex system that provides an amplified fluorescence response for highly sensitive and selective detection of trypsin. In aqueous solution, the functionalized pyrene formed fluorescent, π-extended aggregates inside micelles, which were effectively quenched by protamine (a trypsin substrate). However, this quenched fluorescence was very sensitively recovered by the trypsin's enzymatic reaction, and this was attributed to a marked reduction in enhanced exciton migration caused by protamine in π-delocalized pyrene aggregates. The devised sensing platform was successfully utilized to selectively and sensitively detect trypsin at very low concentrations (0.03-0.5 µg mL-1) in non-pretreated human urine and to screen for trypsin inhibitors at concentrations of 0.1-5.0 µg mL-1.

Protic Ionic Liquids for Intrinsically Stretchable Conductive Polymers.

Inspired by the classic hard-soft acid-base theory and intrigued by a theoretical prediction of spontaneous ion exchange between poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and hard-cation-soft-anion ionic liquid (IL), we treat PEDOT:PSS with a new IL composed of a protic (i.e., extremely hard) cation (3-methylimidazolium, p-MIM+) and an extremely soft anion (tetracyanoborate, TCB-). In fact, this protic IL (p-MIM:TCB) accomplishes the same levels of ion-exchange-mediated PEDOT-PSS separation, PEDOT-rich nanofibril formation, and electrical conductivity enhancement (∼2500 S/cm) as its aprotic counterpart (EMIM:TCB with 1-ethyl-3-methylimidazolium), the best IL used for this purpose so far. Furthermore, p-MIM:TCB significantly outperforms EMIM:TCB in terms of improving the stretchability (i.e., the highest tensile strain) of the PEDOT:PSS thin film. This enhancement is a result of the aromatic and protic cation p-MIM+, which acts as a molecular adhesive holding the exchanged ion pairs (PEDOT+:TCB----p-MIM+:PSS-) via ionic intercalation (at the surface of TCB--decorated PEDOT+ clusters) and hydrogen bonding (to PSS-), in which washing p-MIM+ out of the film degrades the stretchability while keeping the morphology. Our results offer molecular-level insight into the morphological, electrical, and mechanical properties of PEDOT:PSS and a molecular-interaction-based enhancement strategy that can be used for intrinsically stretchable conductive polymers.

Flexible Organic Photodetectors with Mechanically Robust Zinc Oxide Nanoparticle Thin Films.

Zinc oxide nanoparticle (ZnO-NP) thin films have been intensively used as electron transport layers (ETLs) in organic optoelectronic devices, but their moderate mechanical flexibility hinders their application to flexible electronic devices. This study reveals that the multivalent interaction between ZnO-NPs and multicharged conjugated electrolytes, such as diphenylfluorene pyridinium bromide derivative (DFPBr-6), can significantly improve the mechanical flexibility of ZnO-NP thin films. Intermixing ZnO-NPs and DFPBr-6 facilitates the coordination between bromide anions (from the DFPBr-6) and zinc cations on ZnO-NP surfaces, forming Zn2+-Br- bonds. Different from a conventional electrolyte (e.g., KBr), DFPBr-6 with six pyridinium ionic side chains holds the Br--chelated ZnO-NPs adjacent to DFP+ through Zn2+-Br--N+ bonds. Consequently, ZnO-NP:DFPBr-6 thin films exhibit improved mechanical flexibility with a critical bending radius as low as 1.5 mm under tensile bending conditions. Flexible organic photodetectors with ZnO-NP:DFPBr-6 thin films as ETLs demonstrate reliable device performances with high R (0.34 A/W) and D* (3.03 × 1012 Jones) even after 1000 times repetitive bending at a bending radius of 4.0 mm, whereas devices with ZnO-NP and ZnO-NP:KBr ETLs yield >85% reduction in R and D* under the same bending condition.

Conjugated polyelectrolyte dendrimers: aggregation, photophysics, and amplified quenching.

Conjugated polyelectrolyte dendrimers (CPDs) are monodisperse macromolecules that feature a fully π-conjugated dendrimer core surrounded on the periphery by ionic solubilizing groups. CPDs are soluble in water and polar organic solvents, and they exhibit photophysics characteristic of the π-conjugated chromophores comprising the dendrimer core. Here we describe the synthesis and photophysical characterization of series of three generations of CPDs based on a phenylene ethynylene repeat unit structure that is surrounded by an array of anionic sodium carboxylate groups. Molecular dynamics simulations indicate that the first-generation CPD is flat while the second- and third-generation CPDs adopt oblate structures. Photophysical studies, including absorption, fluorescence spectroscopy, and lifetimes, show that the ester protected precursor dendrimers exhibit highly efficient blue fluorescence in THF solution emanating from the phenylene ethynylene chromophore that is in the dendrimer core. By contrast, the water-soluble CPDs have much lower fluorescence quantum yields and the absorption and fluorescence spectra exhibit features of strong chromophore-chromophore interactions. The results are interpreted as suggesting that the CPDs exist as dimer or multimer aggregates, even in very dilute solution. Fluorescence quenching of the anionic CPDs with the dication electron acceptor N,N'-dimethylviologen (MV(2+)) is very efficient, with Stern-Volmer quenching constants (K(SV)) increasing with generation number. The third-generation CPD exhibits highly efficient amplified quenching, with K(SV) ∼ 5 × 10(6) M(-1).

Efficient Imidazolium-Biomolecule Interaction-Assisted Amplified Quenching for Ultrasensitive Detection of Heparin.

Detection of heparin (HP) under physiological conditions is difficult due to the presence of biological obstructions including proteins and lipids. Thus, it is highly challenging to selectively detect HP and to increase its sensitivity in complex systems. Here, we report the detection of HP at nanomolar levels via efficient imidazolium-HP interaction-assisted fluorescence quenching amplification. The self-assembled pyrenyl aggregates are devised as a conduit for efficient exciton transport, which induces amplified fluorescence quenching for HP detection. This amplified quenching is enhanced by introducing an imidazolium receptor designed to have a high affinity to HP via electrostatic and/or additional interactions with C2 protons, resulting in a very high Stern-Volmer quenching constant of approximately 1.17×108  M-1 .

Interfacial morphology and photoelectrochemistry of conjugated polyelectrolytes adsorbed on single crystal TiO2.

The nanoscale morphology and photoactivity of conjugated polyelectrolytes (CPEs) deposited from different solvents onto single crystal TiO(2) were investigated with atomic force microscopy (AFM) and photocurrent spectroscopy. CPE surface coverages on TiO(2) could be incremenentally increased by adsorbing the CPEs from static solutions. The solvents used for polymer adsorption influenced the surface morpohology of the CPEs on the TiO(2) surface. Photocurrent spectroscopy measurements in aqueous electrolytes, using iodide as a hole scavenger, revealed that the magnitude of the sensitized photocurrents was related to the surface coverages and the degree of aggregation of the CPEs as determined by AFM imaging. Absorbed photon-to-current efficiencies approaching 50% were measured for CPE layers as thick as 4 nm on TiO(2). These results suggest that precise control of CPE morphology at the TiO(2) interface can be achieved through optimization of the deposition conditions to improve the power conversion efficiencies of polymer-sensitized solar cells.

A micellized fluorescence sensor based on amplified quenching for highly sensitive detection of non-transferrin-bound iron in serum.

A novel, micelle-based fluorescence system capable of selective and sensitive signal transduction for non-transferrin-bound iron (NTBI) in serum was devised. We demonstrated that an aggregated fluorogenic core in a micelle induces amplified fluorescence quenching, which differentiates this sensing platform from the numerous fluorescence-based tools previously developed for sensitive detection.

A ratiometric fluorescence sensor based on enzymatically activatable micellization of TPE derivatives for quantitative detection of alkaline phosphatase activity in serum.

A novel ratiometric fluorescence assay via enzymatically activatable micellization in aqueous solution was devised for quantitative detection of alkaline phosphatase (ALP) activity. We demonstrated that the dephosphorylation of the water-soluble, phosphate-functionalized, fluorophore monomer P-TPE-TG, induced by an enzymatic reaction of ALP, leads to micelle formation in aqueous solution because its water-soluble functionality is reduced. The dephosphorylation-induced micellization of P-TPE-TG exhibited a ratiometric sensing response for various ALP concentrations (10-200 mU mL-1) and provided a suitable sensing platform for naked eye detection with increased fluorescence quantum yield (Φ = 3.2%), even compared to a typical TPE-based sensor (Φ = 1.0%), where ALP can be sensed with a detection limit of 0.034 mU mL-1. In addition, P-TPE-TG displayed excellent sensing performance at concentrations from 0 to 50 mU mL-1 in diluted human serum (10%), which offers the capability to exploit ratiometric responses for bioactive substances under practical conditions.

Micellization-induced amplified fluorescence response for highly sensitive detection of heparin in serum.

Fluorescence-based assays should be feasible in aqueous media for effectively detecting the biological factors. However, numerous sensors have limited signal transductions and low fluorescence quantum yields due to the ingerently reduced excited state energy of fluorophores in aqueous solution, which reduces their sensitivity. This necessitates a smart sensing approach with an amplified fluorescence response for analytes in aqueous solution. Herein, a new building block which self-assembles in aqueous media, giving a micellar sturcuture with the hydrophobic π-extended conjugated system at the core and hydrophilic groups at the periphery, was devised for the first time. We demonstrated that the aggregated fluorophores in a micelle induce amplified fluorescence quenching, in which the excited electron efficiently migrates through π-extended conjugated system in a micelle, as in a polymeric system. Such feature differentiates this sensing approach from the numerous fluorescence-based tools previously developed for sensitive detection. This new system exhibited highly sensitive signal transduction for specific analytes even under actual bioanalytical conditions.

Influence of abutment connections and plaque control on the initial healing of prematurely exposed implants: an experimental study in dogs.

BACKGROUND: Spontaneous early implant exposure is believed to be harmful, resulting in early crestal bone loss around submerged implants. The purpose of this study was to examine the influence of abutment connections and plaque control on the initial healing of prematurely exposed implants in the canine mandible. METHODS: Bilateral, edentulated, flat alveolar ridges were created in the mandible of 10 mongrel dogs. After 3 months of healing, two implants were placed on each side of the mandible following a commonly used two-stage surgical protocol. Implants on each side were randomly assigned to one of two procedures: 1) connection of a cover screw to the implant and removal of the gingiva to expose the cover screw; and 2) connection of a healing abutment to the implant so that the coronal portion of the abutment remained exposed to the oral cavity. In five dogs (plaque control group), meticulous plaque control was performed. In the other five dogs (no plaque control group), plaque was allowed to accumulate. At 8 weeks post-implantation, microcomputed tomography was performed at the implantation site to measure bone height in the peri-implant bone. RESULTS: The plaque control group had greater vertical alveolar ridge height (9.7 +/- 0.5 mm) than the group without plaque control (7.4 +/- 0.7 mm; P <0.05). In the plaque control group, the average bone height was greater with the abutment-connected implant (10.1 +/- 0.5 mm) than with the partially exposed implant (9.3 +/- 0.5 mm; P <0.05). In the group without plaque control, the average bone height was greater with the partially exposed implant (8.2 +/- 0.6 mm) than with the abutment-connected implant (6.5 +/- 0.7 mm; P <0.05). CONCLUSION: These results suggest that the placement of healing abutments and meticulous plaque control may limit bone loss around submerged implants when implants are partially exposed.

Platelet-enriched fibrin glue and platelet-rich plasma in the repair of bone defects adjacent to titanium dental implants.

PURPOSE: The aim of this study was to compare the effects of platelet-enriched fibrin glue and platelet-rich plasma (PRP) on the repair of bone defects adjacent to titanium dental implants. MATERIALS AND METHODS: In 6 mongrel dogs, 3 screw-shaped titanium dental implants per dog were placed into the osteotomy sites in the tibia. Before implantation, a standardized gap (2.0 mm) was created between the implant surface and the surrounding bone walls. Six gaps were left empty (control group), 6 gaps were filled with autogenous particulate bone mixed with PRP (PRP group), and 6 gaps were filled with autogenous particulate bone mixed with platelet-enriched fibrin glue (fibrin glue group). RESULTS: After 6 weeks, the bone-implant contact was 59.7% in the fibrin glue group, 29.2% in the PRP group, and 10.2% in the control defects; this difference was statistically significant (P < .05). DISCUSSION AND CONCLUSION: Greater bone-implant contact was achieved with platelet-enriched fibrin glue than with PRP. The results indicate that platelet-enriched fibrin glue can induce a stronger peri-implant bone reaction than PRP in the treatment of bone defects adjacent to titanium dental implants.

Ingestion of orthodontic anchorage screws: an experimental study in dogs.

INTRODUCTION: Sharp-edged foreign bodies that are accidentally swallowed can become lodged in the stomach. This animal study was undertaken to determine the outcome of orthodontic anchorage screw ingestion. METHODS: We evaluated radiographs of 10 mixed-breed dogs that ingested 10 orthodontic anchorage screws and 10 reamers (1 screw and 1 reamer per dog). RESULTS: All orthodontic anchorage screws and all but 2 reamers were spontaneously passed within 7 days. CONCLUSIONS: Further investigation is needed to determine whether the results of our animal study agree with clinical findings.

Nerve regeneration with the use of a poly(l-lactide-co-glycolic acid)-coated collagen tube filled with collagen gel.

AIM: The aim of this study was to develop a novel artificial nerve conduit and to evaluate its efficiency based on the promotion of peripheral nerve regeneration in rabbits. MATERIAL AND METHODS: The nerve conduit was made of a poly (l-lactide-co-glycolic acid)-coated collagen tube filled with collagen gel. The conduits were implanted into a 15 mm gap in the peroneal nerves of five rabbits. On the contralateral side, the defects were bridged with collagen-filled vein grafts. RESULTS: Twelve weeks postoperatively nerve regeneration was superior to the vein graft in the PLGA-coated collagen tube, both morphologically and electrophysiologically. CONCLUSION: The results indicate the superiority of the PLGA-coated collagen tube over vein grafts. Furthermore, they show that entubulation repair with this type of tube can support nerve regeneration over a nerve gap distance of at least 15 mm.