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Three functional pyrazinyl pyrazolate Pt(II) complexes [Pt(fprpz)2] (1), [Pt(2fprpz)2] (2), and [Pt(5fprpz)2] (3), each with CF3, CF2H, and C2F5 substituents on pyrazolate, were synthesized from tr...

Gold nanorods (GNRs) with desired longitudinal localized surface plasmon resonance (LLSPR) and strong scattering intensity are important for extending their practical applications in bioimaging and sensing. Herein, a simple additive (HCl and Na2S)-regulated overgrowth approach has been proposed for preparing GNRs with tunable LLSPR. In this approach, HCl is used to slow down the growth reaction rate by changing chemical equilibrium, while Na2S is utilized to halt the reaction when LLSPR is reaching the expected wavelength under monitoring by a UV-Vis spectrometer. Under optimal conditions, GNRs with an LLSPR range from 850 to 650 nm could be facilely prepared with a high precision of 3 nm deviation. The TEM images reveal that GNRs have high monodispersity, displaying an increase in both length and diameter but a decrease in the aspect ratio. With the increase in size, the produced GNRs show enhanced scattering intensity and are applicable for single nanoparticle imaging due to the enlarged absorption and scattering cross-section and improved matching efficiency toward the CCD response.

Citrate-capped gold nanoparticles (AuNPs) modified with thrombin-binding aptamer are often implemented for colorimetric, fluorescent, and electrochemical detection of thrombin in an aqueous solution. However, researchers have rarely explored the application of fibrinogen-modified AuNPs (F-AuNPs) for thrombin sensing. We present a simple, inexpensive, sensitive, and selective probe for colorimetric assay of thrombin through combining thrombin-induced inclusion of F-AuNPs into Fibrin and F-AuNPs-catalyzed reduction of 4-nitrophenol with an excess amount of NaBH4. Considering that fibrinogen stabilized citrate-capped AuNPs against a high-ionic-strength buffer, F-AuNPs efficiently catalyzed the NaBH4-mediated decrease of yellow 4-nitrophenol to colorless 4-aminophenol. The presence of thrombin converted fibrinogen into fibrin on the nanoparticle surface, leading to the inclusion of nanoparticles into fibrin. The formation of fibrin inhibited that the AuNPs catalyzed the NaBH4-mediated reduction of 4-nitrophenol. Consequently, the color of the solution gradually varied from colorless to yellow with increasing thrombin concentration. The proposed system was shown to be accurate in the quantification of small differences in the concentration of human thrombin over the range of 4–60 pM. The lowest detectable concentration of human thrombin by the naked eye was as low as 16 pM. We demonstrated the practical application of the proposed system in quantifying 1–15 nM human thrombin in human plasma.

Gold nanorods (GNRs) with desired longitudinal localized surface plasmon resonance (LLSPR) and strong scattering intensity are important for extending their practical applications in bioimaging and sensing. Herein, a simple additive (HCl and Na

To minimize the need for complex testing procedures, sophisticated instrumentation, and electricity for on-site testing, we demonstrate a simple and portable gold nanocluster (AuNC)-modified paper analytical device integrated with syringe-driven fluid flow to enable highly sensitive mercury ion (Hg2+) detection for environmental monitoring. The device is composed of a paper substrate modified with fluorescent AuNCs (AuNC-paper), which is held within a reusable cartridge connected to a syringe, thus allowing users to flow a large volume of the sample solution through the paper test for greater accumulation of the analyte signal. The metallophilic d10-d10 interaction of Hg2+ with Au+ on the surface of the AuNC-paper induces fluorescence quenching, which can be monitored using a smartphone. Importantly, the red-emitting AuNCs avoid interference with the background fluorescence of the paper substrate. Additionally, the AuNCs are strongly-attached to the paper substrate via carbodiimide coupling, which helps prevent the AuNCs from leaching and enables a large amount of solution to interact with the test (up to 2.5 mL) to increase the amount of the target ions that react with the AuNC-paper. As a result, without the need for preconcentrating the test solution, this paper device can provide the highly sensitive detection of Hg2+ ions, including a 26-fold higher sensitivity than the AuNC-modified test paper without a fluidic cartridge, at a low level of down to nM. The paper platform can complete the detection of Hg2+ ions within 30 min, with a detection limit as low as 1.2 nM, which is less than the United States Environmental Protection Agency’s regulatory limit for drinking water. This highly sensitive, selective, portable, and easy-to-operate platform may be valuable for on-site mercury pollution monitoring in resource-constrained settings.

We report citrate-capped platinum nanoparticles (Pt NPs) as oxidase mimetics for effectively catalyzing the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB), 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), dopamine, and methylene blue in the presence of O 2 . To confirm oxidase-like activity of citrate-capped Pt NPs, their activity toward oxygen reduction reaction was studied using cyclic voltammetry and rotating ring-disk electrode method. The results obtained showed that Pt NP NPs can catalyze the oxidation of organic substrates to the colored product and the reduction of oxygen to water through a four-electron exchange process. Because the aggregation of Pt NPs can inhibit their oxidase-like activity and protamine can recognize heparin, we prepared the protamine-modified Pt NPs through direct adsorption on the surface of citrate-capped Pt NPs. The electrostatic attraction between heparin and protamine-stabilized Pt NPs induced nanoparticle aggregation, inhibiting their catalytic activity. Therefore, the lowest detectable heparin concentrations through UV–vis absorption and by the naked eye were estimated to be 0.3 and 60 nM, respectively. Moreover, the proposed system enabled the determination of the therapeutic heparin concentration in a single drop of blood.

Most of the previously reported studies have focused on the change in the size, morphology, and composition of metal nanocatalysts for improving their catalytic activity. Herein, we report poly(diallyldimethylammonium chloride) [PDDA]-stabilized nanoparticles (NPs) of platinum (Pt) and palladium (Pd) as highly active and efficient catalysts for hydrogenation of 4-nitrophenol (4-NP) in the presence of NaBH4. PDDA-stabilized Pt and Pd NPs possessed similar particle size and same facet with citrate-capped Pt and Pd NPs, making this study to investigate the inter-relationship between catalytic activity and surface ligand without the consideration of the effects of particle size and facet. Compared to citrate-capped Pt and Pd NPs, PDDA-stabilized Pt and Pd NPs exhibited excellent pH and salt stability. PDDA could serve as an electron acceptor for metal NPs to produce the net positive charges on the metal surface, which provide strong electrostatic attraction with negatively charged nitrophenolate and borohydride ions. The activity parameter and rate constant of PDDA-stabilized metal NPs were higher than those of citrate-capped metal NPs. Compared to the previously reported Pd nanomaterials for the catalysis of NaBH4-mediated reduction of 4-NP, PDDA-stabilized Pd NPs exhibited the extremely high activity parameter (195s-1g-1) and provided excellent scalability and reusability.

In present study, we discovered unusual solvent-mediated aggregation-enhanced emission (AEE) character of 11-mercaptoundecanoic acid capped gold nanoclusters (MUA-Au NCs). When aggregated in aqueous media, the MUA-Au NCs showed strong emission, which was weakened by adding ethanol. Interestingly, the suppressed emission was selectively enhanced in the presence of hydrogen sulfide (H2S) because H2S was absorbed onto Au NCs through the strong sulfur-gold bonding affinity. The hydrolyzed H2S, namely, HS−, made the Au NCs negatively charged, which aggregated again due to decreased solubility. The H2S-mediated fluorescence enhancement can be further amplified by introducing a hydrophilic thiolate (glutathione, GSH) onto the surface of Au NCs (GSH/MUA-Au NCs), which enabled sensitive determination of H2S. Under the optimized condition, a detection limit of 35 nM was achieved. The determination was not interfered by other anions such as F−, Cl−, Br−, I−, OAc−, N3−, NO3−, HCO3−, SCN−, SO32−, and SO42−. This excellent sensing performance allowed practical application of the GSH/MUA-Au NC-based sensing platform to accurate determination of H2S in human serum samples.

Cystic dystrophy in heterotopic pancreas (CDHP) is characterized by the presence of cystic dilatation of the ectopic pancreatic ducts in heterotopic pancreas, which mostly occurs in the second portion of the duodenum [1,2].

Protection/deprotection of thiolates are widely used for the design of sensing systems by producing free sulfydryl (–SH) groups. However, most conventional protection/deprotection strategies reported so far suffer poor protection and/or difficult release of –SH group. In this study, phosphorylation/dephosphorylation strategy that exhibits efficient protection and facile liberation of –SH group via the formation of a phosphate-thiol ester, was utilized to develop colorimetric probe for alkaline phosphatase (ALP) activity evaluation. The proposed probe was composed of a cysteamine S-phosphate as a model thiolate substrate and Zonyl FSN-100 functionalized gold nanoparticles (FSN-AuNPs) as reporters. In the presence of ALP, the cysteamine S-phosphate hydrolyzed to generate cysteamine, which aggregated FSN-AuNPs with detectable spectroscopic changes through nanointerface interactions. The changes in UV–vis absorption spectroscopy allowed a detection limit of ALP at 0.1 unit/L. The specific enzyme catalytic hydrolysis provided high selectivity toward ALP over other proteins, small molecules, and metal ions. The practicability of the sensor was validated by accurate examination of ALP in blood samples. In addition, by integrating the conventional ELISA technique and the proposed phosphorylation tactic, sensitive immunoglobulin G detection was achieved.

Citrate-capped gold nanoparticles (AuNPs) modified with thrombin-binding aptamer are often implemented for colorimetric, fluorescent, and electrochemical detection of thrombin in an aqueous solution. However, researchers have rarely explored the application of fibrinogen-modified AuNPs (F-AuNPs) for thrombin sensing. We present a simple, inexpensive, sensitive, and selective probe for colorimetric assay of thrombin through combining thrombin-induced inclusion of F-AuNPs into Fibrin and F-AuNPs-catalyzed reduction of 4-nitrophenol with an excess amount of NaBH

The main symptoms of gastroesophageal reflux disease GERD are heartburn and acid regurgitation. Proton-pump inhibitors (PPI) are considered to be safe and effective for the treatment of GERD. In traditional Chinese medicine, wu chu yu tang (WCYT) is used to treat nausea after eating, vomiting, and diarrhea.We designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the therapeutic effect of WCYT on GERD using omeprazole as a PPI for the positive control.Ninety patients with GERD were randomly assigned to the 1) control group (CG), who received an oral administration of omeprazole (20 mg) once per day and given WCYT placebo (3.0 g) three times per day for 4 weeks continuously; or the 2) treatment group (TG), who received oral administration of omeprazole (20 mg) placebo once per day and WCYT (3.0 g) three times per day for 4 weeks continuously.Seventy-seven patients (37 in CG, 40 in TG) completed the trial. Both Reflux Disease Questionnaire (RDQ) and Gastroesophageal Reflux Disease Questionnaire (GERDQ) scores was less in the second assessment (V2) and in the third assessment (V3) than those in V1 (first assessment; baseline) in the CG and TG groups (all p 0.001); the score difference of both RDQ and GERDQ between V2 and V1 was similar between CG and TG (p = 1.00, p = 0.54, respectively). The score difference of both RDQ and GERD between V3 and V1 was less in the CG group than those of the TG group (both p = 0.004).WCYT has an effect similar to omeprazole for GERD treatment. Furthermore, this effect resulting from WCYT appeared to be maintained for a longer period of time than did that of omeprazole. A study with a larger sample size and longer study period is needed to corroborate our findings.

Summary Pseudoachalasia, or secondary achalasia, caused by neoplasms is a rare entity. We describe a case of pseudoachalasia in an 80-year-old woman who presented with a 2-month history of progressive dysphagia and postprandial vomiting. An esophagogram demonstrated a markedly dilated esophagus with a typical “bird-beak” appearance of the gastroesophageal junction, indicative of achalasia. However, esophageal manometric study disclosed normal peristalsis of the esophagus, not suggestive of a typical feature of achalasia. Abdominal computed tomography scan demonstrated a hypovascular tumor in the left lobe of the liver, extending to the gastroesophageal junction and proximal lesser curve of the stomach. The patient underwent a palliative gastrostomy with a liver biopsy. Finally, cholangiocarcinoma was diagnosed based on the pathological findings. Despite its rarity, clinicians should be aware of this finding as a potential cause of dysphagia in elderly patients.

This study describes the synthesis of fluorescent polydopamine dots (PDs) through hydroxyl radical-induced degradation of polydopamine nanoparticles. The decomposition of polydopamine nanoparticles to fluorescent PDs was confirmed using transmission electron microscopy and dark-field microscopy. The analysis of PDs by using laser desorption/ionization time-of-flight mass spectrometry revealed that the PDs consisted of dopamine, 5,6-dihydroxyindole, and trihydroxyindole units. Oligomerization and self-assembly of these units produced a broad adsorption band, resulting in an excitation-wavelength-dependent emission behavior. The maximal fluorescence of PDs appeared at 440 nm with a quantum yield of 1.2%. The coordination between the catechol groups of PDs and ferric ions (Fe(3+)) quenched the fluorescence of PDs; the limit of detection at a signal-to-noise ratio of 3 for Fe(3+) was determined to be 0.3 μM. The presence of pyrophosphate switched on the fluorescence of the PD-Fe(3+) complexes. Compared to the other reported methods for sensing Fe(3+), PDs provided simple, low-cost, and reusable detection of Fe(3+).

We present a simple, one-pot approach for synthesizing ultrafine platinum (Pt) nanoclusters (NCs) under alkaline conditions using lysozyme (Lys) as a template. From the analysis of the nanoclusters by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Lys VI-stabilized Pt NCs majorly consisted of Pt4 clusters. The formation of Pt NCs was confirmed using X-ray photoelectron spectroscopy and Fourier-transformed infrared spectroscopy. The maximal fluorescence of Pt NCs appears at 434 nm with a quantum yield of 0.08, a fluorescence lifetime of 3.0 ns, and excitation-dependent emission wavelength behavior. Pt NCs exhibit an intrinsic oxidase-like activity because Pt NCs can catalyze O2 oxidation of organic substrates through a four-electron reduction process. Compared with larger Pt nanoparticles, the Pt NCs produce substantially greater catalytic activity in the O2-mediated oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), 3,3',5,5'-tetramethylbenzidine, and dopamine.

Core etching of gold nanoparticles (AuNPs) into smaller-sized clusters is a classic method for fabricating gold nanoclusters (AuNCs). The top down-based synthesis of AuNCs includes two steps: (i) reducing the Au(3+) precursor solution to generate AuNPs in the presence of protecting ligands and (ii) core etching of the formed AuNPs into the AuNCs via ligand exchange. For the first time, this paper describes a one-step approach for preparing AuNCs using a top down approach. The sinapinic acid (SA)-induced formation of the AuNCs involved a three-step reaction process. First, large AuNPs (200 nm) were quickly formed after mixing SA and the Au(3+) precursor solution. Second, excess SA molecules self-assembled on the NP surface, and large AuNPs were etched to small AuNPs via electrostatic repulsion between the neighboring SA molecules. Finally, SA-induced core etching of the AuNPs resulted in the formation of the AuNCs within 70 min. Furthermore, we showed that the presence of the AuNCs in SA was capable of suppressing crystal growth and eliminating the coffee-ring effect. Thus, proteins can be successfully quantified using the SA-AuNCs as matrices for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Compared with using SA as matrices, the SA-AuNCs offered substantial advantages for improving shot-to-shot reproducibility and enhancing the ionization efficiency of proteins.

We report that magnetite nanoparticles (Fe3O4 NPs) act as an efficient quencher for boron dipyrromethene-conjugated adenosine 5'-triphosphate (BODIPY-ATP) that is highly fluorescent in bulk solution. BODIPY-ATP molecules attached to the surface of Fe3O4 NPs through the coordination between the triphosphate group of BODIPY-ATP and Fe(3+)/Fe(2+) on the NP surface. The formed complexes induced an apparent reduction in the BODIPY-ATP fluorescence resulting from an oxidative-photoinduced electron transfer (PET) from the BODIPY-ATP excited state to an unfilled d shell of Fe(3+)/Fe(2+) on the NP surface. A comparison of the Stern-Volmer quenching constant between Fe(3+) and Fe(2+) suggests that Fe(3+) on the NP surface dominantly controls this quenching process. The efficiency for Fe3O4 NP-induced fluorescence quenching of the BODIPY-ATP was enhanced by increasing the concentration of Fe3O4 NPs and lowering the pH of the solution to below 6.0. We found that pyrophosphate and ATP compete with BODIPY-ATP for binding to Fe3O4 NPs. Thus, we amplified BODIPY-ATP fluorescence in the presence of increasing the pyrophosphate and ATP concentration; the detection limits at a signal-to-noise ratio of 3 for pyrophosphate and ATP were determined to be 7 and 30 nM, respectively. The Fe3O4 NP-based competitive binding assay detected ATP and pyrophosphate in only 5 min. The selectivity of this assay for ATP over metal ions, amino acids, and adenosine analogues is particularly high. The practicality of using the developed method to determine ATP in a single drop of blood is also validated.

Background Transarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively. High costs with adverse events (AE) of sorafenib might limit sorafenib dosage, further affecting therapeutic response. To attain greatest benefit, we evaluated the efficacy of different doses and effect of TACE during and after sorafenib discontinuation in patients representing Child-Pugh Classification Class A with venous or extra-hepatic invasion. Methods A total 156 patients met the criteria and were divided into Groups I (n = 52) accepting 800 mg/day; II (n = 58) accepting 800 mg/day and reduced to 400 mg/day owing to AE; and III (n = 46) accepting 400 mg/day. TACE was performed during and after sorafenib discontinuation and therapeutic response bimonthly to four-monthly was rated thereafter. Results Median duration of sorafenib treatment and patients’ survival were 4.00 ± 0.45 and 7.50 ± 1.44 months in all cases; 2.50 ± 0.90 and 5.00 ± 1.10 months in Group I; 5.50 ± 1.27 and 16.50 ± 1.86 months in Group II; 4.00 ± 0.94 and 6.50 ± 2.49 months in Group III. Group II presented the best response and survival benefit (p = 0.010 and p = 0.011 respectively). Child-Pugh Classification score 5 (Hazard Ratio = 0.492, p = 0.049), absent AE (3.423, p = 0.015), tumor numbers ≤ 3 (0.313, p = 0.009), sorafenib duration ≤ 1 cycle (3.694, p = 0.004), and absent TACE (3.197, p = 0.008) significantly correlated with patient survival. TACE benefit appeared in separate and total cases during (p = 0.002, p = 0.595, p = 0.074, p = 0.002 respectively) and after discontinuation of sorafenib administration (p = 0.001, p = 0.034, p = 0.647, p = 0.001 respectively). Conclusions Low-dosage sorafenib not only appeared tolerable and lowered economic pressure but also provided satisfactory results. TACE benefited patient’s survival during and after sorafenib discontinuation.

We report a fluorescence approach for the highly selective and sensitive detection of catecholamines using magnetite nanoparticles (Fe 3 O 4 NPs) in the presence of Amplex UltraRed (AUR) and H 2 O 2 . Fe 3 O 4 NPs catalyze H 2 O 2 -mediated oxidation of AUR. The resulting product fluoresces (excitation/emission maxima, ca. 568/587 nm) more strongly, relative to AUR. When catecholamines bind to Fe 3 O 4 , the complexes that are formed induce decreased activity of Fe 3 O 4 NPs, mediated through the coordination between Fe 3+ on the NP surface and the catechol moiety of catecholamines. As a result, Fe 3 O 4 NPs-catalyzed H 2 O 2 -mediated oxidation of AUR is inhibited by catecholamines. The limits of detection for dopamine (DA), l -DOPA, norepinephrine, and epinephrine were 3 nM, 3 nM, 3 nM, and 6 nM, respectively. The Fe 3 O 4 NPs-H 2 O 2 -AUR probe exhibited high selectivity (>1000-fold) toward catecholamines over other tested biomolecules that commonly exist in urine. Four catecholamines had similar sensitivity because the inhibition of the Fe 3 O 4 NPs activity relies on the presence of the catechol moiety. This approach also allowed the determination of tyrosinase activity because tyrosinase catalyzes the conversion of l -tyrosine to l -DOPA. We validated the practicality of the use of the Fe 3 O 4 NPs-H 2 O 2 -AUR probe for the determination of the concentrations of DA in urine samples.

Bifidobacterium and Lactobacillus can beneficially affect the host by producing acetic acid and lactic acid, which lower pH and thereby inhibit the growth of pathogens or allow the probiotic bacteria to compete with pathogens for epithelial adhesion sites and nutrients. The transmural migration of enteric organisms into the peritoneal cavity can cause peritonitis in peritoneal dialysis (PD) patients. We hypothesized that the composition of the intestinal microbiota with regard to Lactobacillus species and Bifidobacterium species differed between PD patients and healthy controls. The aim of the study was to investigate these differences by real-time PCR analysis of fecal samples. From 1 August 2009 to 31 March 2010, a total of 29 nondiabetic PD patients and 41 healthy controls from China Medical University Hospital were recruited after giving their informed consent. Fecal samples were collected from the PD patients and their age-matched counterparts in the morning using a standardized procedure. DNA extracted from these samples was analyzed by real-time PCR. All bifidobacteria, Bifidobacterium catenulatum , B. longum , B. bifidum , Lactobacillus plantarum , L. paracasei , and Klebsiella pneumoniae were less frequently detected in the patient samples. Dysbiosis (microbial imbalance) may impair intestinal barrier function and increase host vulnerability to pathogen invasion. Further studies are necessary to confirm our findings before clinical trials with probiotic supplementation in PD patients.

Rational Lymphangiomatosis is rare and benign, and slowly proliferating lymphatic vessels of unknown etiology and visceral lymphangiomatosis involving the spleen is rare. Since lymphangiomatosis may be asymptomatic or present as a sense of fullness, splenic cystic lymphangiomatosis is a disease of little concern. Patient concerns A 34-year-old woman suffering from progressive epigastric fullness after oral intake for two weeks. Diagnoses Physical examination showed a palpable mass which was more than 10 cm in size over the left hypochondrium. An abdominal computed tomography disclosed marked splenomegaly with multiple cystic lesions in the spleen, causing external compression with right-sided deviation of the adjacent organs and varices in the upper abdomen. Esophagogastroduodenoscopy revealed portal hypertensive gastropathy. Interventions Conventional total splenectomy was performed in this patient because of an enlarged spleen and unknown etiology, preoperatively. Upon surgery, splenomegaly with polycystic content and varicose vessels over the omentum were noted. Autologous spleen transplantation was not performed because of limited orthotopic and vascularized spleen. Outcomes The patient is doing well 18 months after splenectomy. Lessons This was a rare case presenting with splenic cystic lymphangiomatosis in association with omental varices and portal hypertension. Splenic cystic lymphangiomatosis should be considered in the differential diagnosis of patients with a palpable painless mass over the left hypochondrium.

In this paper, we present a simple and rapid colorimetric assay--using the polythymine oligonucleotide T(33), citrate-capped gold nanoparticles (AuNPs), and phosphate-buffer saline (PBS) in the presence of Mn(2+)--for the highly selective and sensitive detection of Hg(2+) in an aqueous solution. Citrate-capped AuNPs adsorbed on randomly coiled T(33) were dispersed well in PBS because of strong electrostatic repulsion between DNA molecules. In the presence of Hg(2+), the formation of Hg(2+)-T(33) complexes enabled the removal of T(33) molecules from the NP surface, resulting in salt-induced NP aggregation. However, the T(33)-capped AuNPs (T(33)-AuNPs) were dispersed in PBS solution after the addition of 1.0 microM Hg(2+), indicating that T(33)-AuNPs had poor colorimetric sensitivity toward Hg(2+). We uncovered that the addition of Mn(2+) to a solution containing 0.75 nM T(33)-AuNPs and 0.2x PBS resulted in an acceleration of the analysis time (within 5 min) and a 100-fold sensitivity improvement for the detection of Hg(2+). As a result, the present approach enables the analysis of Hg(2+) with a minimum detectable concentration that corresponds to 10 nM. This is probably attributed to that Mn(2+) binds strongly to the phosphate backbone of DNA, thereby accelerating Hg(2+)-induced aggregation of the T(33)-AuNPs. Because Mn(2+) can stabilize the folded structure of the Hg(2+)-T(33) complex, Hg(2+) facilitates the removal of T(33) from the NP surface in the presence of Mn(2+). This probe was successfully applied to the determination of Hg(2+) in pond water.

Citrate-capped gold nanoparticles (AuNPs) serve as matrices for the determination of biomolecules in a high-salt solution through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In the case of using 2,5-dihydroxybenzoic acid (2,5-DHB) as a matrix, the signal intensities of neutral steroids were severely suppressed in a high-salt solution. A high concentration of NaCl caused the formation of the sodium adduct ions during the desorption/ionization process, resulting in a decrease of the signal intensities of the protonated ions. In comparison, by applying AuNP-assisted LDI-TOF-MS, the signal intensities of neutral steroids remained almost constant when the concentration of NaCl was increased to 500 mM. Because the use of citrate-capped AuNPs as matrices primarily offers alkali metal ion adducts, AuNP matrices have a higher tolerance to high NaCl concentrations relative to that of 2,5-DHB matrices. The relevant phenomena are also discovered in the case of analysis of neutral carbohydrate, monosialoganglioside, indolamine, and angiotensin I. The quantification of small molecules in a high-salt solution has been accomplished by AuNP-assisted LDI-TOF-MS coupled to a unique sample preparation, in which samples are deposited onto the sample plate before AuNPs. The present method has been further applied to the determination of urea, creatinine, uric acid, and glucose in a urine sample.

Objective: To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange. Case Summary: A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patient's jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment. Discussion: Angiotensin-converting enzyme (ACE) inhibitor–induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor–induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure. Conclusions: Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.

A new colorimetric sensor for sensing Hg2+ in a high-salinity solution has been developed using gold nanoparticles (AuNPs) decorated with 3-mercaptopropionate acid (MPA) and adenosine monophosphate (AMP). Because of the high negative charge density of AMP on each AuNP surface, MPA/AMP-capped AuNPs are well dispersed in a high-salt solution. In contrast, the aggregation of MPA-capped AuNPs was induced by sodium ions, which shield the negative charges of the carboxylic groups of MPA. Through the coordination between the carboxylic group of MPA and Hg2+, the selectivity of MPA/AMP-capped AuNPs for Hg2+ in a high-salt solution is remarkably high over that of the other metals without the addition of a masking agent or a change in the temperature. We have carefully investigated the effect of the AMP concentration on the stability and sensitivity of MPA/AMP-capped AuNPs. Under optimum conditions, the lowest detectable concentration of Hg2+ using this probe was 500 nM on the basis of the measurement of the ratio of absorption at 620 nm to that at 520 nm. The sensitivity to Hg2+ can be further improved by modifying the MPA/AMP-capped AuNPs with highly fluorescent rhodamine 6G (R6G). By monitoring the fluorescence enhancement, the lowest detectable concentration of Hg2+ using R6G/MPA/AMP-capped AuNPs was 50 nM.

We present a simple approach for on-line concentration of SDS-protein complexes by using poly(vinyl alcohol) (PVA) solution in CGE. In comparison to the coated capillary, the presence of EOF in CGE omitted the need to fill the capillaries with polymer solutions prior to the analysis. More importantly, we found that highly reproducible separation of eight proteins by 3.5% PVA was achieved between runs and without the regeneration of high bulk EOF; the RSD of migration times was less than 0.7%. To further improve the concentration sensitivity, neutral PVA was introduced into the capillary with the help of EOF to act as sieving matrix. The occurrence of stacking at the boundary between the PVA and the sample zone is mainly due to the retardation of proteins by PVA. As a result, the LODs at an S/N of 3 for SDS-protein complexes are of the order of sub-nM to several nM. For example, the LOD for BSA is 0.78 nM, which is a 91-fold sensitivity enhancement over the normal injection. In addition, our stacking method has been applied to the analyses of proteins in Escherichia coli cells. The peak for beta-galactosidase (E. coli) was observed after 0.1 microM beta-galactosidase was spiked into the E. coli samples.

Primary Klebsiella pneumoniae liver abscess with metastatic complications is a globally emerging infectious disease and is the leading cause of liver abscess in Taiwan. Host immunity and bacterial virulence, especially of the capsular polysaccharide type, are important in determining clinical manifestations. Investigators retrospectively studied the K pneumoniae genotype and capsular serotype from patients with 37 strains of liver abscess; no correlation was noted with genotype, and many genetically different strains caused liver abscess. Although K pneumoniae is prevalent in patients with diabetes, it can attack healthy or alcoholic people as well. Additional studies are needed to explore the mechanisms of bacterial virulence and to optimize treatment strategies. Physicians should be alert to the illness and its complications.

We report an online concentration and separation method for basic proteins using poly(diallyldimethylammonium chloride) (PDDA) solutions in the presence of reversed EOF. Using a capillary dynamically coated with 2% PDDA containing 0.1 M NaCl and filled with 1.2% PDDA under neutral conditions (10 mM phosphate, pH 7.0), we have demonstrated the separation of six basic proteins with peak efficiencies ranging from 175 000 to 616 000 plates/m and RSDs of migration time less than 0.4%. Additionally, high-speed separation of six basic proteins (

Background and Aim: To compare the efficacy and safety of endoscopic variceal ligation (EVL) with propranolol in prophylaxis on the rate of first esophageal variceal bleeding in patients with cirrhosis. Methods: A prospective, randomized trial was conducted in 100 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Results: Life-table curves showed that prophylactic EVL and propranolol were similarly effective for primary prophylaxis of variceal bleeding (11/50 [22%]vs 12/50 [24%]; P = 0.68) and overall mortality (14/50 [28%]vs 12/50 [24%]; P = 0.49). The 2-year cumulative bleeding rate was 18% (9/50) in the EVL group and 16% (8/50) in the propranolol group. The 2-year cumulative mortality rate was 28% (14/50) in the EVL group and 24% (12/50) in the propranolol group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed no significant difference in mortality in both groups (P = 0.86). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. In the propranolol group, the mean daily dosage of the drug was 68.2 ± 32.8 mg, which was sufficient to reduce the pulse rate by 25%. 20% of patients withdrew from propranolol treatment due to adverse events. Conclusions: Prophylaxis EVL is as effective and as safe as treatment with propranolol in decreasing the incidence of first variceal bleeding and death in cirrhotic patients with high-risk esophageal varices.

This study describes a simple method for removing mercuric ions (Hg(2+)) from a high-salt matrix based on the use of Tween-20-stabilized gold nanoparticles (Tween 20-Au NPs) as Hg(2+) adsorbents and composites of reduced graphite oxide and Fe3O4 NPs as NP collectors. Citrate ions adsorbed on the surface of the Tween 20-Au NPs reduced Hg(2+) to Hg(0), resulting in the deposition of Hg(0) on the surface of the NPs. To circumvent time-consuming centrifugation and transfer steps, the Hg(0)-containing gold NPs were collected using reduced graphite oxide-Fe3O4 NP composites. Compared with the reported NP-based methods for removing Hg(2+), Tween 20-Au NPs offered the rapid (within 30 min), efficient (99% elimination efficiency), durable (10 cycles), and selective removal of Hg(2+), CH3Hg(+), and C2H5Hg(+) in a high-salt matrix without the interference of other metal ions. This was attributed to the fact that the dispersed Tween 20-Au NPs exhibited large surface-area-to-volume ratio to bind Hg(2+) through Hg(2+)-Au(+) metallophilic interactions in a high-salt matrix. The formation of graphite oxide sheets and reduced graphite oxide-Fe3O4 NP composites was demonstrated using X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectrometry, and transmission electron microscopy. The mechanism of interaction between Tween 20-Au NPs and Hg(2+) was studied using visible spectroscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy.

Background/Purpose: Effective mediators activate downstream transducers regulating inflammation and angiogenesis. Correlation among mediators IL-6, IL-27, TNF-α, and VEGF with STAT proteins at diverse clinical-pathologic stages of cirrhotic patients remains limited. Methods: Plasma mediators were assayed from 158 naïve liver cirrhosis (LC-total group) and 144 non-LC individuals. The LC-total group included 69 hepatitis B virus-infected (LC-HBV) patients, 40 hepatitis C virus-infected (LC-HCV) patients, and 49 patients without HBV−/HCV− infection (LC-NBNC). Another 144 non-LC individuals comprised 54 healthy persons (HG) and 90 chronic hepatitis patients (CH-total) as the control group. To correlate with plasma mediators, 52 paired liver tissues (CH: 41 and LC: 11 cases) served for p-STAT1 and p-STAT3 immunostaining. Results: Although IL-6, IL-27, TNF-α, and VEGF were expressed significantly in CH-total versus HG (p = 0.011, p

Aims Effective cytokines can drive the commitment of naive T cells to regulate immune response after antigen-mediated activation. Aims are to elucidate the clinical role of serum IL-27 and IL-6 in the different stages of naive hepatitis B virus (HBV)-infected patients. Methods Samples with well-characterized clinical profiles were assessed from 395 HBV-infected patients including chronic hepatitis B (CHB) group in 291 patients, liver cirrhosis (LC) group in 57 patients, hepatocellular carcinoma (HCC) group in 47 patients. Another 139 non-HBV infected individuals were enrolled as control group (CG) including 104 with normal liver function (NF) and 35 with liver dysfunction (LD). Results The HBV-infected group and separated groups presented significantly higher IL-27 and IL-6 expression than the CG or subgroups of CG. In contrast to IL-27, IL-6 showed significant differences with deteriorating liver condition compared with LC or HCC with CHB groups. Furthermore, IL-6, rather than IL-27, showed significant statistical differences in patients with advanced liver disease compared with those of mild or moderate to severe liver disease and in patients with terminal stage HCC compared with those of early to intermediate or advanced stage HCC. The data associated with liver function, including Albumin, Bilirubin, INR, Platelet and AFP levels, were significantly correlated to IL-6 expression, but had weak correlation to IL-27 expression in HBV patients. Conclusion Serum IL-27 can trigger immune response to prevent hepatic injury in different clinical-pathologic stages of HBV-infected patients earlier, but IL-6 may play an extremely important role to determine the liver progression.

We have developed a rapid and homogeneous method for the highly selective detection of Hg(2+) and Ag(+) using Tween 20-modified gold nanoparticles (AuNPs). Citrate ions were found to still be adsorbed on the Au surface when citrate-capped AuNPs were modified with Tween 20, which stabilizes the citrate-capped AuNPs against conditions of high ionic strength. When citrate ions had reduced Hg(2+) and Ag(+) to form Hg-Au alloys and Ag on the surface of the AuNPs, Tween 20 was removed from the NP surface. As a result, the AuNPs were unstable under a high-ionic-strength solution, resulting in NP aggregation. The formation of Hg-Au alloys or Ag on the surface of the AuNPs was demonstrated by means of inductively coupled plasma mass spectroscopy and energy-dispersive X-ray spectroscopy. Tween 20-AuNPs could selectively detect Hg(2+) and Ag(+) at concentrations as low as 0.1 and 0.1 microM in the presence of NaCl and EDTA, respectively. Moreover, the probe enables the analysis of AgNPs with a minimum detectable concentration that corresponds to 1 pM. This probe was successfully applied to detect Hg(2+) in drinking water and seawater, Ag(+) in drinking water, and AgNPs in drinking water.

We report a one-pot synthesis of poly(diallyldimethylammonium chloride)-coated Fe 3 O 4 (PDDA-Fe 3 O 4 ) nanoparticles (NPs) by the coprecipitation method. The formed PDDA-Fe 3 O 4 NPs were characterized by powder X-ray diffraction and superconducting quantum interference device. The crystalline structure and superparamagnetic property of PDDA-Fe 3 O 4 NPs were found to be similar to those of Fe 3 O 4 NPs, indicating that the presence of PDDA does not affect the formation of Fe 3 O 4 NPs. Moreover, glucose oxidase (GOx) and citrate-capped gold (Au) NPs, having negative charges, can be easily self-assembled at the surface of cationic PDDA-Fe 3 O 4 NPs. Without the requirement of a peroxidise enzyme, the composites of PDDA-Fe 3 O 4 NPs and GOx effectively catalyzes the H 2 O 2 -mediated oxidation of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate acid) (ABTS) in the presence of glucose. This colorimetric method enables the analysis of glucose with a minimum detectable concentration that corresponds to 30 μM. We validate the applicability of this method by determining the concentration of glucose in serum samples. In another application, the composites of PDDA-Fe 3 O 4 and Au NPs were shown to be capable of selectively enriching cysteine-containing peptides through the formation of Au–S bonds. The extracted peptides can be easily detected by matrix-assisted laser desorption/ionization-time of flight mass spectrometer. Both applications open up a new way for the synthesis of bifunctional NPs.

The purpose of this study was to examine the roles of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-18, and alpha-fetoprotein (AFP) in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC).AFP and cytokine serum concentrations were determined via EIA or ELISA.In total, 81 patients were included, including 9 healthy controls, 36 LC patients, and 36 HCC patients. Significant differences in AFP, TNF-alpha, IL-6, and IL-18 between the three groups were noted (p0.001). AFP was lowest in the healthy subjects, intermediate in LC patients and highest in HCC patients (all p0.001). 11-6 and 11-18 concentrations were significantly higher in the HCC group than the other two groups. HCC and LC patients with AFP concentration7ng/ml had increased IL-18 concentrations compared to both the other groups p0.001). In contrast to previously published studies, TNF-alpha was highest in the healthy group, intermediate in the HCC group, and lowest in the LC group (p0.001).IL-18 may be a potential tumour marker in combination with IL-6 and AFP in the diagnosis of HCC, but further research including a larger population of patients is essential. Further research is warranted.

Background GI stromal tumors (GISTs), with their potential for malignant transformation, are usually treated by surgical intervention. Endoscopic treatment remains controversial. Objective The aim of this study was to investigate clinical outcomes associated with use of endoscopic ligation and resection for diagnosis and treatment of small EUS-suspected gastric GISTs. Design Prospective case series. Setting Academic medical center. Patients Eight patients with submucosal gastric tumors Interventions Endoscopic ligation and resection. Main Outcome Measurements Clinical/technical feasibility, success, and adverse events. Results Seven patients with small EUS-suspected gastric GISTs were successfully treated by endoscopic ligation, with sloughing of residual tissue within 1 month. All were diagnosed pathologically with GISTs of low malignant potential. One additional patient required a second ligation to remove residual tumor, also diagnosed as a GIST with low malignant potential. No perforation, massive hemorrhage, or other complication requiring endoscopic or surgical intervention occurred. Limitations Small number of patients (n = 8) and limited follow-up; risk of microscopically positive margins, which limits application to lesions strongly suspected to be benign. Conclusions Endoscopic ligation and resection shows promise as a safe and feasible technique to treat small EUS-suspected gastric GISTs. Controlled clinical trials with more subjects and longer follow-up are needed to confirm the value and limitations of this method.

We have developed a colorimetric assay for the highly sensitive and selective detection of Pb(2+) by narrowing the size distribution of gallic acid-capped gold nanoparticles (GA-AuNPs) and minimizing electrostatic repulsion between each GA-AuNP. We unveil that the particle size and size distribution of GA-AuNPs could be controlled by varying the pH of HAuCl(4) with fixed concentrations of HAuCl(4) and GA. When the pH of the precursor solution (i.e., HAuCl(4)) was adjusted from 2.2 to 11.1, the average diameter of GA-AuNPs was decreased from 75.1 nm to 9.3 nm and their size distribution was reduced from 56.6-93.6 nm to 9.0-9.6 nm. The colorimetric sensitivity of the Pb(2+)-induced aggregation of GA-AuNPs could be improved using narrow size distribution of GA-AuNPs. Moreover, further enhancement of the colorimetric sensitivity of GA-AuNPs toward Pb(2+) could be achieved by adding NaClO(4) to minimize electrostatic repulsion between GA-AuNPs, which provide a small energy barrier for Pb(2+) to overcome. Under the optimum conditions (1.0 mM NaClO(4) and 20 mM formic acid at pH 4.5), the selectivity of 9.3 nm GA-AuNPs for Pb(2+) over other metal ions in aqueous solutions is remarkably high, and its minimum detectable concentration for Pb(2+) is 10nM. We demonstrate the practicality of 9.3 nm GA-AuNPs for the determination of Pb(2+) in drinking water. This approach offers several advantages, including simplicity (without temperature control), low cost (no enzyme or DNA), high sensitivity, high selectivity, and a large linear range (10.0-1000.0 nM).

The simultaneous separation of anionic and cationic proteins has been achieved by addition of high concentration of poly(diallyldimethylammonium chloride) (PDDAC) in capillary electrophoresis. A capillary was filled with PDDAC so that it would act as ion-pair reagents in the separation of anionic proteins. On the other hand, the PDDAC can also be used as coating additives for the analysis of cationic proteins. Increasing the concentration of PDDAC in the separation buffer had the ability to improve the separation efficiency, change the electrophoretic mobility, and alter the separation selectivity; however, this was not true in the case of analyzing proteins by using the PDDAC larger than 1.6%. By both using a buffer containing 1.6% PDDAC and applying pH-stepwise techniques, 13 proteins with a wide range of pI (4.7-11.1) and molecular masses (6.5-198.0 kDa) could be separated within 30 min in a single run. In addition to this separation, we observed not only more peaks from alpha-chymotrypsinogen A and aprotinin but also the bovine serum albumin (BSA) dimer and trimer. With the 50 nL protein injection sample, the limits of detections at signal-to-noise of 3 for proteins are in the range of 0.07-0.79 microM. Except for BSA, the relative standard derivation values of migration time and peak height for all proteins were1.3 and6.9%, respectively. We suggested that this proposed method is a promising approach for clinical diagnosis and proteomics applications.

We present the first example of the analysis of acidic and basic proteins by nanoparticle-filled capillary electrophoresis. Compared to the didodecyldimethylammonium bromide (DDAB)-coated capillary, the DDAB-capped gold nanoparticles (AuNPs) as pseudostationary phase were found to form more stable coating on the capillary wall, thus leading to greater separation efficiency and high reproducibility. In addition to their advantages for protein separation, DDAB-capped AuNPs can generate high reversed electroosmotic flow, which is 75% greater than DDAB at pH 3.5. To allow strong interactions with proteins, the AuNPs were modified with poly(ethylene oxide) via noncovalent bonding to form gold nanoparticles/polymer composites (AuNPPs). Using a capillary dynamically coated with DDAB-capped AuNPs and filled with AuNPPs under acidic conditions (10 mM phosphate, pH 3.5), we have demonstrated the separation of acidic and basic proteins with peak efficiencies ranging from 71 000 to 1 007 000 plates/m and relative standard deviations of migration time less than 0.6%. Additionally, the proposed method has been applied to the analyses of biological samples, including saliva, red blood cells, and plasma. With simplicity, high resolving power, and high reproducibility, the proposed method has shown great potential for proteomics applications and clinical diagnosis.

A 68-year-old man presented to our hospital with a 2-day history of upper abdominal pain and non-bilious vomiting. Twenty years previously he had undergone a subtotal gastrectomy with Billroth II reconstruction because of a gastric ulcer. He denied alcohol consumption or trauma. Physical examination revealed that his upper abdomen was tender with muscle guarding and rebound tenderness. Laboratory tests showed the following: haemoglobin 11 g/dl (normal, 14–16 g/dl), white blood count 12.9×109/l …