Elucidating the Mechanisms of Sodium Benzoate in Alzheimer Disease: Insights from Quantitative Proteomics Analysis of Serum Samples.

BACKGROUND: N-methyl-D-aspartate receptors (NMDARs) are crucial components of brain function involved in memory and neurotransmission. Sodium benzoate is a promising NMDAR enhancer and has been proven to be a novel, safe, and efficient therapy for patients with Alzheimer disease (AD). However, in addition to the role of sodium benzoate as an NMDA enhancer, other mechanisms of sodium benzoate in treating AD are still unclear. To elucidate the potential mechanisms of sodium benzoate in Alzheimer disease, this study employed label-free quantitative proteomics to analyze serum samples from AD cohorts with and without sodium benzoate treatment. METHODS: The serum proteins from each patient were separated into 24 fractions using an immobilized pH gradient, digested with trypsin, and then subjected to nanoLC‒MS/MS to analyze the proteome of all patients. The nanoLC‒MS/MS data were obtained with a label-free quantitative proteomic approach. Proteins with fold changes were analyzed with STRING and Cytoscape to find key protein networks/processes and hub proteins. RESULTS: Our analysis identified 861 and 927 protein groups in the benzoate treatment cohort and the placebo cohort, respectively. The results demonstrated that sodium benzoate had the most significant effect on the complement and coagulation cascade pathways, amyloidosis disease, immune responses, and lipid metabolic processes. Moreover, Transthyretin, Fibrinogen alpha chain, Haptoglobin, Apolipoprotein B-100, Fibrinogen beta chain, Apolipoprotein E, and Alpha-1-acid glycoprotein 1 were identified as hub proteins in the protein‒protein interaction networks. CONCLUSIONS: These findings suggest that sodium benzoate may exert its influence on important pathways associated with AD, thus contributing to the improvement in the pathogenesis of the disease.

New Insights on Volatile Components of Vanilla planifolia Cultivated in Taiwan.

Vanilla (Vanilla planifolia) is a precious natural flavoring that is commonly used throughout the world. In the past, all vanilla used in Taiwan was imported; however, recent breakthroughs in cultivation and processing technology have allowed Taiwan to produce its own supply of vanilla. In this study, headspace solid-phase microextraction (HS-SPME) combined with GC-FID and GC-MS was used to analyze the volatile components of vanilla from different origins produced in Taiwan under different cultivation and processing conditions. The results of our study revealed that when comparing different harvest maturities, the composition diversity and total volatile content were both higher when the pods were matured for more than 38 weeks. When comparing different killing conditions, we observed that the highest vanillin percentage was present after vanilla pods were killed three times in 65 °C treatments for 1 min each. From the experiment examining the addition of different strains, the PCA results revealed that the volatiles of vanilla that was processed with Dekkera bruxellensis and Bacillus subtilis was clearly distinguished from which obtained by processing with the other strains. Vanilla processed with B. subtilis contained 2-ethyl-1-hexanol, and this was not detected in other vanillas. Finally, when comparing the vanillin percentage from seven different regions in Taiwan, vanilla percentage from Taitung and Taoyuan Longtan were the highest.

Effects of acute heat stress on protein expression and histone modification in the adrenal gland of male layer-type country chickens.

The adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 roosters were subject to acute heat stress and thereafter classified into a resistant or susceptible group according to body temperature change. The iTRAQ analysis identified 80 differentially expressed proteins, in which the resistant group had a higher level of somatostatin and hydroxy-δ-5-steroid dehydrogenase but a lower parathymosin expression in accordance with the change of serum glucocorticoid levels. Histone modification analysis identified 115 histone markers. The susceptible group had a higher level of tri-methylation of histone H3 lysine 27 (H3K27me3) and showed a positive crosstalk with K36me and K37me in the H3 tails. The differential changes of body temperature projected in physiological regulation at the hypothalamus-pituitary-adrenal axis suggest the genetic heterogeneity in basic metabolic rate and efficiency for heat dissipation to acclimate to thermal stress and maintain body temperature homeostasis. The alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal gland and may contribute to the thermotolerance of chickens.

PON-1 carbamylation is enhanced in HDL of uremia patients.

High-density lipoprotein (HDL) carbamylation has been known in uremia patients. Paraoxonase-1 (PON-1) is an important HDL protein responsible for HDL anti-oxidant, arylesterase and lactonase activities. PON-1 carbamylation in uremic HDL has never been explored. We isolated HDL from uremia patients and control healthy subjects for study. Sandwich ELISA was used to estimate carbamylated PON-1 protein expression in HDL, and nanoflow liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) was applied to identify the amino acid in PON-1 carbamylated. PON-1 enzyme activities were estimated by substrates conversion method. HDL anti-oxidant activity was gauged by fluorescence changes of indicator dye in the presence of H2O2. Our study results proved that the degree of PON-1 carbamylation was higher in uremic HDL than in control HDL. Sandwich ELISA study showed that carbamylated PON-1 concentration in uremic HDL was 1.49 ± 0.08 fold higher than that in HDL from controls (p < 0.05). The nanoLC-MS/MS showed that the carbamylation of lysine 290 (K290) of PON-1, a residue adjacent to PON-1 activity determining site, was detected in uremic HDL but not detected in control HDL. K290 carbamylation leads to local conformation changes that reduce accessible solvent accessibility. The HDL paraoxonase, arylesterase, and lactonase activities were all significantly lower in uremia patients than in control subjects. Additionally, HDL anti-antioxidant ability was also lower in uremia patients. Carbamylation of PON-1 in uremia patients could be one of the factors in impairing PON-1 enzyme activities and HDL anti-oxidation function.

Effect of Seasonal Change on Testicular Protein Expression in White Roman Geese.

The purpose of this study was to investigate the change in protein expression in the testes of ganders at various breeding stages. A total of nine 3-year-old male White Roman ganders were used. The blood and testis samples were collected at the nonbreeding, sexual reactivation, and breeding stages for sex hormone analysis and proteomic analysis, respectively. The testicular weight and serum testosterone observed for ganders at the breeding stage were higher than those for ganders at nonbreeding and sexual reactivation stages (P < 0.05). There were 124 protein spots differentially expressed in the testes of ganders at various reproductive stages. A total of 107 protein spots of 74 proteins was identified through mass spectrometry. Most of the differentially expressed proteins were responsible for the molecular functions of protein binding (24%) and catalytic activity (16%). A functional pathway analysis suggested that proteins involved in steroidogenesis, metabolism, and spermatogenesis pathways changed in the White Roman geese at various reproductive stages. In conclusion, ganders at various reproductive stages exhibited different levels of testosterone and protein expression in the testes. The varied levels of the proteins might be essential and unique key factors in seasonal reproduction in ganders.

Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients.

Diabetic nephropathy (DN) is a major complication in diabetic patients. Microalbuminuria testing is used to identify renal disease; however, its predictive value is questionable. We aimed to identify urinary biomarkers to early diagnosis nephropathy before identifiable alternations in kidney function or urine albumin excretion occurs. Proteomic approaches were used to identify potential urinary biomarkers and enzyme-linked immunosorbent assay was performed to verify the results. The data identified haptoglobin (HPT) and α-1-microglobulin/bikunin precursor (AMBP) as two biomarkers with the highest ability to distinguish between healthy individuals and patients with nephropathy, and between diabetic patients with and without DN. Further, the HPT-to-creatinine ratio (HCR) was evaluated as an independent predictor of early renal functional decline (ERFD) in a cohort with an average follow-up of 4.2 years. The area under the curve (AUC) value for ERFD prediction was significantly improved when the HCR biomarker was included in the model with albumin to creatinine ratio (ACR) and baseline characteristics (AUC values were 0.803 and 0.759 for HCR and ACR, respectively; p value was 0.0423 for difference between models). In conclusion, our results suggest that HCR represents an early indicator of nephropathy, and a marker related to ERFD among diabetic patients in Taiwan.

Increased electronegativity of high-density lipoprotein in uremia patients impairs its functional properties and is associated with the risk of coronary artery disease.

BACKGROUND AND AIMS: Uremia patients have impaired high-density lipoprotein (HDL) function and a high risk of coronary artery disease (CAD). Increased lipoprotein electronegativity can compromise lipoprotein function, but the effect of increased HDL electronegativity on HDL function and its association with CAD in uremia patient are not clear. We aimed to assess HDL electronegativity and various properties of HDL in uremia patients and investigate whether electronegative HDL is a risk factor for CAD in these individuals. METHODS: HDL from 60 uremia patients and 43 healthy controls was separated into 5 subfractions (H1H5) with increasing electronegativity by using anion-exchange chromatography. Lipoprotein content was analyzed by gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry. HDL anti-oxidant, anti-apoptosis and cholesterol efflux activities were examined by fluorescence-based assays. RESULTS: The percentage of H5 HDL (H5%) was significantly higher in uremia patients than in controls (p < 0.001). The concentration of apolipoprotein (Apo) AI was lower and apolipoprotein modifications were more prevalent in uremia HDL subfractions than in control HDL subfractions. Carbamylation of ApoAI and ApoCIII was increased in more electronegative HDL subfractions from uremia patients. Anti-oxidant activity, anti-apoptotic activity, and cholesterol efflux capability were reduced in HDL subfractions from uremia patients when compared with control HDL subfractions. Multiple logistic regression analysis showed that H5% was associated with CAD risk in uremia patients. CONCLUSIONS: In HDL of uremia patients, increased electronegativity is accompanied by compositional changes and impaired function. Our findings indicate that increased H5% is associated with increased CAD risk in uremia patients.

Urine proteome analysis by C18 plate-matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows noninvasive differential diagnosis and prediction of diabetic nephropathy.

Diabetic nephropathy (DN) is one of the most common complications in diabetic patients. New noninvasive markers are still needed for the early detection of DN before identifiable alternations in kidney function or urine albumin excretion occurs. A C18 plate and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to compare the urinary protein profiles of 238 subjects from the following 4 groups: patients with type 2 diabetic (T2D) with microalbuminuria, patients with DM without micro- or macroalbuminuria, patients with micro- or macroalbuminuria due to nondiabetic disease, and healthy controls. ß2-microglobulin (B2M) and Clara-cell protein (CC16) were found to be highly released in the urine of patients with proteinuria due to nondiabetic or diabetic diseases. In differentiating nephropathy from healthy subject, the B2M and CC16 markers have a combined sensitivity and specificity of 77.3% and 91.8%, respectively. In distinguishing T2D with microalbuminuria from T2D patients, the combined markers have sensitivity and specificity of 66% and 73%, respectively. The predictive ability of B2M and CC16 for early renal functional decline (ERFD) was validated in 125 T2D patients with a follow-up times. The odds ratio (OR) of combined B2M and CC16 markers for developing ERFD was 7.59 (95% CI: 1.97-29.24). The detection of B2M and CC16 with the C18 plate-MALDI-TOF MS approach could be an attractive and practical assay for rapid diagnosis of nephropathy in nondiabetic/diabetic patients and as a predictor of ERFD among T2D patients who had not manifested significant kidney disease at baseline.

Infrared spectra and anharmonic coupling of proton-bound nitrogen dimers N2-H+-N2, N2-D+-N2, and 15N2-H+-15N2 in solid para-hydrogen.

The proton-bound nitrogen dimer, N2-H+-N2, and its isotopologues were investigated by means of vibrational spectroscopy. These species were produced upon electron bombardment of mixtures of N2 (or 15N2) and para-hydrogen (p-H2) or normal-D2 (n-D2) during deposition at 3.2 K. Reduced-dimension anharmonic vibrational Schrödinger equations were constructed to account for the strong anharmonic effects in these protonated species. The fundamental lines of proton motions in N2-H+-N2 were observed at 715.0 (NH+N antisymmetric stretch, ν4), 1129.6 (NH+N bend, ν6), and 2352.7 (antisymmetric NN/NN stretch, ν3) cm-1, in agreement with values of 763, 1144, and 2423 cm-1 predicted with anharmonic calculations using the discrete-variable representation (DVR) method at the CCSD/aug-cc-pVDZ level. The lines at 1030.2 and 1395.5 cm-1 were assigned to combination bands involving nν2 + ν4 (n = 1 and 2) according to theoretical calculations; ν2 is the N2N2 stretching mode. For 15N2-H+-15N2 in solid p-H2, the corresponding major lines were observed at 710.0 (ν4), 1016.7 (ν2 + ν4), 1124.3 (ν6), 1384.8 (2ν2 + ν4), and 2274.9 (ν3) cm-1. For N2-D+-N2 in solid n-D2, the corresponding major lines were observed at 494.0 (ν4), 840.7 (ν2 + ν4), 825.5 (ν6), and 2356.2 (ν3) cm-1. In addition, two lines at 762.0 (weak) and 808.3 cm-1 were tentatively assigned to be some modes of N2-H+-N2 perturbed or activated by a third N2 near the proton.

The comparison of CHCA solvent compositions for improving LC-MALDI performance and its application to study the impact of aflatoxin B1 on the liver proteome of diabetes mellitus type 1 mice.

In nanoflow liquid chromatography-matrix-assisted laser desorption/ionization tandem time-of-flight (nanoLC-MALDI-TOF/TOF) approaches, it is critical to directly apply small amounts of the sample elutes on the sample target using a nanoLC system due to its low flow rate of 200 ~ 300 nl/min. It is recommended to apply a sheath liquid containing a matrix with a several µL/min flow rate at the end of the nanoLC column to ensure a larger co-eluted droplet for more reproducible sample spotting and avoid the laborious task of post-manual matrix spotting. In this study, to achieve a better nanoLC-MALDI performance on sample spotting, we first compared α-Cyano-4-hydroxycinnamic acid (CHCA) solvent composition for efficiently concentrating nanoLC elutes on an anchor chip. The solvent composition of isopropanol (IPA): acetonitrile (ACN):acetone:0.1% Trifluoroacetic acid (TFA) (2:7:7:2) provided strong and homogeneous signals with higher peptide ion yields than the other solvent compositions. Then, nanoLC-MALDI-TOF/TOF was applied to study the impact of aflatoxin B1 on the liver proteome from diabetes mellitus type 1 mice. Aflatoxin B1 (AFB1), produced by Aspergillus flavus and Aspergillus parasiticus is a carcinogen and a known causative agent of liver cancer. To evaluate the effects of long-term exposure to AFB1 on type 1 diabetes mellitus (TIDM), the livers of T1DM control mice and mice treated with AFB1 were analyzed using isotope-coded protein labeling (ICPL)-based quantitative proteomics. Our results showed that gluconeogenesis, lipid, and oxidative phosphorylation mechanisms, normally elevated in T1DM, were disordered following AFB1 treatment. In addition, major urinary protein 1 (MUP1), an indicator of increased insulin sensitivity, was significantly decreased in the T1DM/AFB1 group and may have resulted in higher blood glucose levels compared to the T1DM group. These results indicate that T1DM patients should avoid the AFB1 intake, as they could lead to increased blood glucose levels and disorders of energy-producing mechanisms.

Tuning the vibrational coupling of H3O+ by changing its solvation environment.

This study demonstrates how the intermode coupling in the hydronium ion (H3O+) is modulated by the composition of the first solvation shell. A series of rare gas solvated hydronium ions (H3O+Rg3, where Rg = Ne, Ar, Kr, and Xe) is examined via reduced-dimensional anharmonic vibrational (RDAV) ab initio calculations. We considered six key vibrational normal modes, namely: a hindered rotation, two H-O-H bends, and three O-H stretches. Between the O-H stretches and the H-O-H bends, the first is more sensitive to solvation strength. Our calculations revealed that the Fermi resonance between the first overtones of O-H bends and the fundamentals of O-H stretches led to complex spectral features from 3000 to 3500 cm-1. Such an interaction is not only sensitive to the type of rare gas messengers surrounding the H3O+ ion, it also exhibits an anomalous H → D isotope effect. Although it is accepted that visible combination tones (∼1900 cm-1) arise from the complex coupling between the hindered rotation and the H-O-H bends, the origin of their intensities is not yet clearly understood. We found that the intensity of these combination tones could be much stronger than their fundamental H-O-H bends. Within our theoretical framework, we tracked the combination tone's intensity back to the asymmetric O-H stretches. This simple notion of intensity borrowing is confirmed by examining eight complexes (H3O+·Rg3 and D3O+·Rg3) with spectral features awaiting experimental confirmations.

Rapid fabrication of functionalized plates for peptides, glycopeptides and protein purification and mass spectrometry analysis.

A rapid and simple approach for fabricating a disposable functionalized membrane on matrix-assisted laser desorption ionization (MALDI) targets, glass, or plastic substrates, without using complex mechanical protocols or chemical reactions, was developed for sample enrichment and mass spectrometry analysis. By coating functionalized-silica particles on a polydimethylsiloxane (PDMS)-coated plate, these particles can form a monolayer of materials on the PDMS membrane for sample handling without peeling off. An octadecyl(C18)-functionalized plate was fabricated by coating porous C18-silica particles on a PDMS-coated plate. The C18 particle-coated PDMS plate (CP plate) has better sensitivity than C18 tips and magnetic nanoparticles, along with a higher sample recovery (64.3 ± 4.9%) compared to the C18 tip method, when analyzing trace amounts of 5 fm BSA digest samples. The CP plate shows significantly higher urea/SDS removal efficiency on the cell lysate proteome compared to C18 tips. The capacity of the C18 spot (∼2.8 mm in diameter) on the CP plate was ∼10 µg of BSA digests. A hydrophilic particle-coated PDMS plate was also fabricated and successfully used for glycopeptide enrichment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis.

Double Filtration Plasma Apheresis Shortens Hospital Admission Duration of Patients With Severe Hypertriglyceridemia-Associated Acute Pancreatitis.

OBJECTIVES: The treatment effectiveness of double filtration plasma apheresis (DFPP) on severe hypertriglyceridemia-associated acute pancreatitis (STAP) has been questioned because the currently defined serum triglyceride level--1000 mg/dL--is too low for STAP. Given this, we aimed to investigate DFPP effectiveness when we elevated STAP definition to 5000 mg/dL serum triglyceride. METHODS: We performed nested case-control studies for STAP patients and divided them into groups "with" or "without" DFPP. We further recruited outpatient asymptomatic hypertriglyceridemia patients with STAP history, then divided them into groups "with" or "without" prophylactic DFPP once every 3 to 6 months for 2 years. We observed hospitalization duration and STAP recurrence between patients with and patients without DFPP. RESULTS: Twelve STAP patients receiving DFPP had a median hospitalization of 5 days, whereas 24 patients without DFPP had 10 days (P = 0.009). Six outpatient referrals with STAP history receiving prophylactic DFPP showed no STAP recurrences whereas 6 without DFPP showed 3 recurrences (P = 0.046). For the 25 patients whose serum triglyceride exceeded 5000 mg/dL, 11 receiving DFPP had median hospitalization of 5 days while 14 without DFPP had 11 days (P = 0.012). CONCLUSIONS: When applied to serum triglyceride in excess of 5000 mg/dL, DFPP removes oxidized and inflammatory lipoproteins, shortens hospitalization duration, and minimizes STAP recurrence.

Early prediction of severe acute pancreatitis by urinary ß-2 microglobulin/saposin B peak ratios on MALDI-TOF.

The current methods for predicting severe acute pancreatitis (severe AP) are either complicated or lack efficient sensitivity and specificity. In this study, a simple and practical approach was developed to predict severe AP by using peak intensity ratio of urinary ß-2 microglobulin (B2M) to saposin B (SB) on MALDI-TOF MS. Patients with B2M/SB ratio higher than 1.127 present severe AP symptom with a higher Ranson score, computed tomography (CT) grade and longer hospitalization with a sensitivity of 83.7% and specificity of 74.3%. Label-free quantitative proteomics by nanoLC-MS/MS was applied to urine of severe AP patients and found that severe AP is accompanied with kidney injury and inflammation. The measurement of B2M/SB ratios by MALDI-TOF MS could be a simple, accurate and rapid method to diagnose severe AP as well as to monitor AP progression.

Biochemical and functional characterization of charge-defined subfractions of high-density lipoprotein from normal adults.

High-density lipoprotein (HDL) is regarded as atheroprotective because it provides antioxidant and anti-inflammatory benefits and plays an important role in reverse cholesterol transport. In this paper, we outline a novel methodology for studying the heterogeneity of HDL. Using anion-exchange chromatography, we separated HDL from 6 healthy individuals into five subfractions (H1 through H5) with increasing charge and evaluated the composition and biologic activities of each subfraction. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that apolipoprotein (apo) AI and apoAII were present in all 5 subfractions; apoCI was present only in H1, and apoCIII and apoE were most abundantly present in H4 and H5. HDL-associated antioxidant enzymes such as lecithin-cholesterol acyltransferase, lipoprotein-associated phospholipase A2, and paraoxonase 1 were most abundant in H4 and H5. Lipoprotein isoforms were analyzed in each subfraction by using matrix-assisted laser desorption-time-of-flight mass spectrometry. To quantify other proteins in the HDL subfractions, we used the isobaric tags for the relative and absolute quantitation approach followed by nanoflow liquid chromatography-tandem mass spectrometry analysis. Most antioxidant proteins detected were found in H4 and H5. The ability of each subfraction to induce cholesterol efflux from macrophages increased with increasing HDL electronegativity, with the exception of H5, which promoted the least efflux activity. In conclusion, anion-exchange chromatography is an attractive method for separating HDL into subfractions with distinct lipoprotein compositions and biologic activities. By comparing the properties of these subfractions, it may be possible to uncover HDL-specific proteins that play a role in disease.

Oxidized ApoC1 on MALDI-TOF and glycated-ApoA1 band on gradient gel as potential diagnostic tools for atherosclerotic vascular disease.

BACKGROUND: Atherosclerotic vascular disease (ASVD), including coronary artery disease, ischemic stroke, and peripheral vascular disease, is the most common cause of death both in the general population and in high-risk patients; patients with diabetes mellitus (DM), uremia (UM), primary hyperlipidemia (HP) have increased risks for developing ASVD. METHODS: To identify new biomarkers for early prediction of ASVD, HDL samples from patients with disease (ASVD) and patients with increased risks but no documented ASVD (non-ASVD) were collected for Bis-Tris gradient gel and MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) analyses. RESULTS: Oxidation of ApoC1 was detected specifically in ASVD samples by MALDI-TOF. On the Bis-Tris gradient gel, non-ASVD ApoA1 was displayed into 2 distinct bands A and B. An additional C band of ApoA1 appeared exclusively in ASVD patients. The extraordinary C band of ApoA1 was characterized by high levels of glycation and oxidation. MALDI-TOF analyses of ApoA1 peptides after trypsin digestion confirmed higher levels of glycation and oxidation levels in the ASVD than non-ASVD samples. CONCLUSIONS: Gel identification of the highly-glycated and oxidized C band of ApoA1 and MALDI-TOF detection of oxidized ApoC1 in HDL may provide a new approach for early ASVD diagnosis.

Mass spectrometry-based plasma peptide profiling of acute exacerbation in HBeAg-positive chronic hepatitis B.

BACKGROUND: Acute exacerbations (AE) of serum alanine aminotransferase activities that are 5 times above the normal upper limit frequently occur during the immune clearance phase of hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB). It is unclear how the varying clinical severities of AE reflect differences in the underlying immune responses against the hepatitis B virus. METHODS: We utilized magnetic bead-based purification methods coupled with MALDI-TOF mass spectrometry to generate plasma peptide profiles from HBeAg-positive CHB patients experiencing AE without and with clinical decompensation. RESULTS: Hydrophobic interaction chromatography (HIC C18) provided a more discriminatory spectral profile than immobilized Cu(2+) metal ion affinity chromatography did for diagnosis of a clinical spectrum of AEs. Using the sorting algorithm, Support Vector Machine, a classification model consisting of 5 classifiers was determined to give a sensitivity of 94.7% and a specificity of 75% for differentiating patients with and without decompensation. Classifiers identified as fragments derived from transthyretin and apolipoprotein A-IV were significantly decreased and increased in patients with decompensation, respectively. CONCLUSIONS: Our study demonstrated that HIC C18 fractionation coupled with MALDI-TOF mass spectrometry can be used for differentiating AE with and without decompensation in patients with HBeAg-positive CHB.

Benzylamine-assisted noncovalent exfoliation of graphite-protecting Pt nanoparticles applied as catalyst for methanol oxidation.

A novel method has been developed to physically exfoliate graphite and uniformly disperse Pt nanoparticles on graphite nanoplates without damaging the graphene structures. A stable aqueous suspension of graphite nanoplates was achieved by benzylamine-assisted noncovalent fuctionalization to graphite and characterized by transmission electron microscopy, X-ray diffraction and Raman spectroscopy. A uniform dispersion of Pt nanoparticles was then prepared on the graphite nanoplates, where the benzylamine acts as a stabilizer. These Pt loaded graphite nanoplates were then prepared as an electrode, which significantly increased catalytic activity toward the methanol oxidation reaction, resulting in a 60% increment in mass activity compared to that of E-TEK.

Gold-catalyzed stereoselective synthesis of azacyclic compounds through a redox/[2 + 2 + 1] cycloaddition cascade of nitroalkyne substrates.

We report a new redox/cycloaddition cascade on readily available 1-alkynyl-2-nitrobenzenes that produces complex azacyclic compounds stereoselectively. The core structures of the resulting products are constructed through a formal [2 + 2 + 1] cycloaddition among α-carbonyl carbenoids, nitroso species, and external alkenes.

Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) relies mainly on histopathological imaging examinations after surgical removal of the tumor. However, the rate of tumor recurrence is still high. Defining molecular signatures comprised of a number of distinct peptide ions specific for various tumor regions may improve the classification and prognosis of HCC patients. METHODS: MALDI imaging technology, cluster analysis and classification software were applied to investigate patients with hepatitis B virus (HBV)-related HCC to obtain differences in protein abundance and distribution from non-tumor to tumor regions. RESULTS: A number of mass spectra obtained from non-tumor and HCC tumor sections were readily distinguishable. Progressive change was found in a distance-dependent manner from non-tumor to tumor regions within the junction section of HCC. Fourteen of the peaks were determined from non-tumor and tumor sections as classifiers to classify various non-tumor and tumor regions of the junction section of HCC. The performance of the classification test for the tumor region with a coefficient of variation (CV) of 0.16 was better than the non-tumor region, which reached a CV of 0.53. CONCLUSIONS: Our findings provide peptide information pertaining to the classification of various tumor regions to supplement current histopathological analysis in tumor margins.