A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

OBJECTIVES: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. METHODS: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. RESULTS: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-Inositol, lactate, L6 lipids ( = CH-CH2-CH = O), L5 lipids (-CH2-C = O), and L3 lipids (-CH2-CH2-C = O) as well as lower levels of β -glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. CONCLUSIONS: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research. These results offer new, sensitive and specific, noninvasive approaches that may be of great benefit to immunoglobulin A nephropathy patients by enabling earlier diagnosis

A geochemical record of the link between chemical weathering and the East Asian summer monsoon during the late Holocene preserved in lacustrine sediments from Poyang Lake, central China

This paper presents relatively high-resolution geochemical records spanning the past 4000 cal yr BP obtained from the lacustrine sediments of Poyang Lake in central China. The variations in the intensity of the East Asian summer monsoon (EASM) are traced using the K/Na, Ti/Na, Al/K, kaolinite/illite and clay/feldspar ratios, together with the chemical index of alteration (CIA), as indicators of chemical weathering. During the last 4000 years, the proxy records of chemical weathering from Poyang Lake exhibit an overall enhanced trend, consistent with regional hydrological changes in previous independent records. Further comparisons and analyses demonstrate that regional moisture variations in central China is inversely correlated with the EASM intensity, with weak EASM generating high precipitation in central China. Our data reveal three intervals of dramatically dry climatic conditions (i.e., ca. 4000-3200 cal yr BP, ca. 2800-2400 cal yr BP, and ca. 500-200 cal yr BP). A period of weak chemical weathering, related to cold and dry climatic conditions, occurred during the Little Ice Age (LIA), whereas more intense chemical weathering, reflecting warm and humid climatic conditions, was recorded during the Medieval Warm Period (MWP). Besides, an intensification of chemical weathering in Poyang Lake during the late Holocene agrees well with strong ENSO activity, suggesting that moisture variations in central China may be predominantly driven by ENSO variability

Petrogenesis of Triassic granite from the Jintan pluton in Central Jiangxi Province, South China: implication for uranium enrichment

Numerous Triassic biotite granites and two-mica granites crop out in the interior of South China, and some of them possess high U contents, which have been regarded as the sources for later hydrothermal mineralization. Their petrogenesis is therefore crucial for constraining the possible origins of the U enrichment. Here we report new LA-ICPMS zircon U-Pb ages, mineral geochemistry of biotite and muscovite, whole rock geochemical results and Sr-Nd and zircon Hf isotope data from the Jintan pluton in Central Jiangxi Province, South China. LA-ICPMS zircon U-Pb dating indicates that both biotite granite (BG) and two-mica granite (TMG) in the Jintan pluton crystallized at similar to 220 Ma. The TMG have higher U contents (7.85 to 48.90 ppm, average 18.44 ppm) than theBG (4.99 to 17.72 ppm, average 8.64 ppm). Both BG and TMG show negative whole-rock epsilon(Nd)(t)and zircon epsilon(Hf)(t)values and contain some inherited zircons. The TMG are strongly peraluminous (A/CNK = 1.13-133), contain abundant primary muscovite, and display S-type affinity on plots of Yvs Rb and Th vs Rb, suggesting that they are S-type granites. The BG also display S-type granite affinities on plots of Yvs Rb and Th vs Rb. The suites display similar Sr-Nd isotope compositions (BG initial Sr-87/(86) Sr values = 0.711389 to 0.714225 and E-Nd(t) = -9.91 to -9.16, TMG initial Sr-87/(86) Sr values = 0.711832 and epsilon(Nd)(t) = -10.02) and are spatially associated, suggesting that the BG should also be classified as S-type granites. The TMG have higher zircon epsilon Hf(t)values (-6.4 to -1.1) than the BG (-8.7 to -3.7), indicating the TMG and BG might be derived from similar sediments but possibly with some distinct characteristics in their sources. The BG exhibit linear covariations in chemical compositions with relatively high total REE and light REE contents and MgO contents, while the TMG displays broader compositional variations but with relatively low total REE, light REE and MgO contents. Biotite geochemistry indicates the TMG formed in a more reduced magmatic system than the BG. The temperatures estimated by zircon saturation thermometry indicate the BG had distinctly higher magmatic temperatures than the TMG. The TMG display relatively high Al2O3/TiO2 ratios and low CaO/Na2O ratios than the BG but have higher Sr/Y and La/Yb ratios. The geochemical and petrological data suggest the BG were derived from clay-poor psammite sources at deeper levels with higher temperatures and higher oxygen fugacity, and underwent an extensive fractional crystallization, while the TMG was derived from clay-rich pelitic sources at higher levels and lower temperatures and oxygen fugacity with only limited fractional crystallization. We conclude that the combination of U-rich sources, physical-chemical conditions such as low partial melting temperature or low degrees of partial melting, a reduced environment and low REE and LREE contents of magmas controlled the U enrichment in TMG. (C) 2018 Elsevier B.V. All rights reserved

Large cooperative effects in tunneling rates across van der Waals coupled binary self-assembled monolayers

This paper describes large positive cooperative effects of two orders of magnitude in the tunneling rates across molecular junctions of mixed self-assembled monolayers (SAMs) of rectifying (ferrocenyl undecanethiol HS(CH2)11Fc) and non-rectifying molecules with different terminal groups (11-undecanethiol and its derivatives, denoted as HS(CH2)11X, where X = -H, -NH2 or -NO2). By gradually diluting the surface fraction of HS(CH2)11Fc in the mixed SAM, it is found that the large positive cooperative effect is only important in the coherent tunneling regime but not in the incoherent tunneling regime. Density functional theory (DFT) shows that the measured cooperative effects in the tunneling rates in these binary systems are caused by Fc---X van der Waals interactions which increase in the order of -H< -NH2< -NO2. These strong cooperative effects dramatically alter the operation of a molecular diode, further highlighting the importance of taking cooperative effects into account, in this case driven by van der Waals interactions, in the rational design of electronic devices working at tunneling regime

Genome-wide analysis of microRNAs expression profiling in patients with primary IgA nephropathy

The aim of this study was to investigate the differential expression characteristics and the roles of the genome-wide microRNAs (miRNAs) in immunoglobulin A nephropathy (IgAN) kidney tissues. We used Illumina high-throughput sequencing technology to evaluate the miRNAs expression of six biopsy tissues from IgAN and six normal renal cortex specimens from patients with renal cell carcinoma. We observed a total of 85 miRNAs that were differentially expressed in the six IgAN patients, of which 11 miRNAs were up-regulated and 74 miRNAs were down-regulated in patients' tissues compared with control tissues. Additionally, we identified 55 candidate novel miRNAs in our study, which comprised seven candidates who were detected in the IgAN group and 49 candidates who were detected in the control group. Only one candidate (miR-n-9) was expressed in both groups. The bioinformatics showed that the regulated target genes of differentially expressed miRNAs were associated with immune and renal pathological changes. The identification of specific tissue miRNAs in our study not only helped clarify the genetics or immunology mechanisms involved in the pathogenesis of IgAN but also helped explain the pathological changes in the kidney tissues. We hypothesize that some significant miRNAs might potentially serve as novel diagnostic biomarkers in IgAN patients