The concentration of dissolved organic matter impacts the neurobehavior in female zebrafish exposed to cyclophosphamide.

Cyclophosphamide (CP) is a broad-spectrum anticancer drug for various cancers and frequently detected in aquatic environments, reaching concentrations up to 22 µg/L. However, there is limited understanding of the toxicities of CP with the presence of dissolved organic matter, a ubiquitous component in aquatic environments, in fish. In this study, we investigated the behaviors, morphological alterations of retina, and related gene transcripts in zebrafish exposed to CP (0 and 50 µg/L) and Humic acid (HA, a main component of DOM) at concentrations of 0, 3, 10, and 30 mg-C/L for 30 days. The results showed that, relative to the zebrafish in CP treatment, HA at 30 mg-C/L increased the locomotion (12.1 % in the light and 7.2 % in the dark) and startle response (9.7 %), while inhibiting the anxiety (12.5 %) and cognition of female zebrafish (24.6 %). The levels of transcripts of neurotransmitter- (tph1b and ache), neuroinflammation-(il-6 and tnfα) and antioxidant-(gpx) related genes in the brain of female adult were also altered by CP with the presence of HA. In addition, HA promoted the transgenerational effects of CP on the neurobehaviors. Therefore, HA can enhance potential neurotoxicity of CP in female fish through alteration neurotransmission related genes. Our findings provide new insights into the toxicity and underlying mechanisms of CP with the presence of dissolved organic matter, thereby contribute to a deeper understanding of the risks posed by CP in aquatic ecosystems.

[A multiscale feature extraction algorithm for dysarthric speech recognition].

In this paper, we propose a multi-scale mel domain feature map extraction algorithm to solve the problem that the speech recognition rate of dysarthria is difficult to improve. We used the empirical mode decomposition method to decompose speech signals and extracted Fbank features and their first-order differences for each of the three effective components to construct a new feature map, which could capture details in the frequency domain. Secondly, due to the problems of effective feature loss and high computational complexity in the training process of single channel neural network, we proposed a speech recognition network model in this paper. Finally, training and decoding were performed on the public UA-Speech dataset. The experimental results showed that the accuracy of the speech recognition model of this method reached 92.77%. Therefore, the algorithm proposed in this paper can effectively improve the speech recognition rate of dysarthria.

Transmission properties of periodically sparse patterned microring resonators.

By using the transfer matrix method, we analyze the optical properties of periodically sparse patterned microring resonators in the resonator-waveguide system. The dispersion relation of a periodically sparse patterned microring is investigated theoretically. Two kinds of modes supported by the periodically sparse patterned microring resonators, traveling modes and stationary modes, are found. We also derive the reflectivity of the microring resonator side-coupled to a waveguide and find that just the stationary modes lead to total reflections. Traveling modes do not reflect, which can be used to extend free spectral range. All the transmission properties are confirmed by the finite-difference time-domain method numerically.

Controllable linear asymmetric transmission and perfect polarization conversion in a terahertz hybrid metal-graphene metasurface.

We propose a three layered metal-graphene-metal metasurface to investigate the controllable linear asymmetric transmission and perfect polarization conversion in THz regime, by using the finite-difference time-domain (FDTD) method. An on-to-off control of asymmetric transmission and perfect polarization conversion is achieved by changing the Fermi energy of graphene from 0.8 eV to 0 eV. We present the electric field distribution and Fabry-Perot-like cavity model to analyze the working mechanisms. By gradually shifting the Fermi energy of graphene, two functions are realized, i.e., controllable linear asymmetric transmission and controllable total transmission with near perfect polarization conversion.

Optical chirality breaking in a bilayered chiral metamaterial.

We propose a planar optical bilayered chiral metamaterial, which consists of periodic metallic arrays of two L-shaped structures and a nanorod twisted on both sides of a dielectric slab, to investigate the optical chirality breaking effect by using finite-difference time-domain (FDTD) method. Even the metamaterial is with chiral symmetry, an optical chirality breaking window in the asymmetric transmission pass band is obtained in chiral metamaterial structure. We analyze the plasmonic mode properties and attribute the mechanism of the optical chirality breaking effect to the plasmonic analogue of EIT. The optical chirality breaking window can be modulated by changing the geometric parameters of the nanorods in the structure.

A new Z-eigenvalue localization set for tensors.

A new Z-eigenvalue localization set for tensors is given and proved to be tighter than those in the work of Wang et al. (Discrete Contin. Dyn. Syst., Ser. B 22(1):187-198, 2017). Based on this set, a sharper upper bound for the Z-spectral radius of weakly symmetric nonnegative tensors is obtained. Finally, numerical examples are given to verify the theoretical results.

A new S-type upper bound for the largest singular value of nonnegative rectangular tensors.

By breaking [Formula: see text] into disjoint subsets S and its complement, a new S-type upper bound for the largest singular value of nonnegative rectangular tensors is given and proved to be better than some existing ones. Numerical examples are given to verify the theoretical results.

The disc separation and the eigenvalue distribution of the Schur complement of nonstrictly diagonally dominant matrices.

The result on the Gersgorin disc separation from the origin for strictly diagonally dominant matrices and their Schur complements in (Liu and Zhang in SIAM J. Matrix Anal. Appl. 27(3):665-674, 2005) is extended to nonstrictly diagonally dominant matrices and their Schur complements, showing that under some conditions the separation of the Schur complement of a nonstrictly diagonally dominant matrix is greater than that of the original grand matrix. As an application, the eigenvalue distribution of the Schur complement is discussed for nonstrictly diagonally dominant matrices to derive some significant conclusions. Finally, some examples are provided to show the effectiveness of theoretical results.

An eigenvalue localization set for tensors and its applications.

A new eigenvalue localization set for tensors is given and proved to be tighter than those presented by Li et al. (Linear Algebra Appl. 481:36-53, 2015) and Huang et al. (J. Inequal. Appl. 2016:254, 2016). As an application of this set, new bounds for the minimum eigenvalue of [Formula: see text]-tensors are established and proved to be sharper than some known results. Compared with the results obtained by Huang et al., the advantage of our results is that, without considering the selection of nonempty proper subsets S of [Formula: see text], we can obtain a tighter eigenvalue localization set for tensors and sharper bounds for the minimum eigenvalue of [Formula: see text]-tensors. Finally, numerical examples are given to verify the theoretical results.

Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy.

BACKGROUND: Monitoring blood uric acid (UA) is important in all patients on urate-lowering therapy so that the selection of the effective drugs and dosage adjustments could be made until the target level is reached. The issue is that frequent needle jabs are unacceptable. Reported mean levels of salivary UA were 185-240 µmol/l in healthy adults. A linear correlation was demonstrated between UA concentrations in saliva and plasma. We monitored salivary UA instead of plasmatic UA in a patient with gout. METHODS: Allopurinol and benzbromarone were used as the therapeutic drugs. Salivary UA; urinary UA and creatinine; and plasmatic UA, creatinine, kynurenine and tryptophan were measured by HPLC. RESULTS: Salivary UA indicated the efficacy of therapy accurately and conveniently. After eight weeks therapy, the weekly mean levels of salivary UA were reduced and maintained to <300 µmol/l, which was equivalent to <360 µmol/l of plasmatic UA according to the salivary UA/plasmatic UA ratio of this patient. CONCLUSION: Measurement of salivary UA is a noninvasive and useful way for monitoring the status of hyperuricemia and the therapeutic efficacy of urate-lowering therapy. It has value for the management of hyperuricemia and gout.

Simultaneous determination of plasma creatinine, uric acid, kynurenine and tryptophan by high-performance liquid chromatography: method validation and in application to the assessment of renal function.

A high-performance liquid chromatography with ultraviolet detection method has been developed for the simultaneous determination of a set of reliable markers of renal function, including creatinine, uric acid, kynurenine and tryptophan in plasma. Separation was achieved by an Agilent HC-C18 (2) analytical column. Gradient elution and programmed wavelength detection allowed the method to be used to analyze these compounds by just one injection. The total run time was 25 min with all peaks of interest being eluted within 13 min. Good linear responses were found with correlation coefficient >0.999 for all analytes within the concentration range of the relevant levels. The recovery was: creatinine, 101 ± 1%; uric acid, 94.9 ± 3.7%; kynurenine, 100 ± 2%; and tryptophan, 92.6 ± 2.9%. Coefficients of variation within-run and between-run of all analytes were ≤2.4%. The limit of detection of the method was: creatinine, 0.1 µmol/L; uric acid, 0.05 µmol/L; kynurenine, 0.02 µmol/L; and tryptophan, 1 µmol/L. The developed method could be employed as a useful tool for the detection of chronic kidney disease, even at an early stage.

Plasma kynurenic acid/tryptophan ratio: a sensitive and reliable biomarker for the assessment of renal function.

BACKGROUND: Decreased tryptophan (TRP) and increased kynurenine (KYN) and kynurenic acid (KYNA) in blood have been reported in patients and experimental animals with renal diseases. We investigated if these compounds could be used as new biomarkers for the assessment of renal function. METHODS: Eighty hospitalized hypertensive patients (20 with chronic kidney disease (CKD), and other 60 were considered as control) were enrolled for the investigation. Plasma TRP, KYN, and KYNA were determined by high-performance liquid chromatography. Change rate (CR) was employed to evaluate the sensitivity of the parameters of renal function. RESULTS: CR of plasma KYNA/TRP ratio (+103%) was much higher than the CRs of blood urea nitrogen (+44%), serum creatinine (+56%) and estimated glomerular filtration rate (-35%). Plasma KYNA/TRP ratio was in close relationship with blood urea nitrogen (r = 0.622), serum creatinine (r = 0.797), urine micro-albumin/24-h (r = 0.518) and estimated glomerular filtration rate (r = -0.662), respectively, with all p-values <0.001. CONCLUSIONS: Plasma KYNA/TRP ratio was sensitive and reliable to indicate renal function and could be used as a new biomarker to assess the risk or presence of kidney disease.

Simultaneous determination of urinary tryptophan, tryptophan-related metabolites and creatinine by high performance liquid chromatography with ultraviolet and fluorimetric detection.

A high performance liquid chromatography method with ultraviolet and fluorimetric detection has been developed for the simultaneous determination of urinary creatinine (Cr), tryptophan (Trp) and three Trp-related metabolites including kynurenine (Kyn), kynurenic acid (Kyna) and 5-hydroxyindole-3-acetic acid (5-HIAA). Samples were pretreated by centrifugation after a freeze-thaw cycle to remove protein and other precipitates. Separation was achieved by an Agilent HC-C18 (2) analytical column and a gradient elution program with a constant flow rate 1mL/min at an ambient temperature. Total run time was 30 min. Cr, Kyn and Kyna were measured by a variable wavelength detector at wavelengths 258 nm, 365 nm and 344 nm respectively. Trp and 5-HIAA were measured by a fluorescence detector with an excitation wavelength of 295 nm and an emission wavelength of 340 nm. This allowed the determination of Kyn/Cr, Kyna/Cr, Trp/Cr and 5-HIAA/Cr concentration ratios in a single run on the same urine sample. Good linear responses were found with correlation coefficient (r)>0.999 for all analytes within the concentration range of physiological level. The limit of detection of the developed method was: Cr, 0.0002 g/L; Kyn, 0.1 µmol/L; Kyna, 0.04 µmol/L; Trp, 0.02 µmol/L and 5-HIAA, 0.01 µmol/L. Recoveries from spiked human urine were: Cr, 93.0-106.4%; Kyn, 97.9-106.9%; Kyna, 98.5-105.6%; Trp, 96.7-105.2% and 5-HIAA, 96.1-99.7%. CVs of repeatability and intermediate precision of all analytes were less than 5%. This method has been applied to the analysis of urine samples from normal subjects.

Optimization of Zn2+-containing mobile phase for simultaneous determination of kynurenine, kynurenic acid and tryptophan in human plasma by high performance liquid chromatography.

In the present work we have developed a standard-addition HPLC method using a mobile phase containing low concentration of ZnAc(2) to determine physiological level of kynurenine (KYN), kynurenic acid (KYNA) and tryptophan (TRP) in human plasma simultaneously. The method greatly improved the sensitivity of KYNA, the resolution of KYNA and TRP, and avoided clotting risk caused by high concentration of ZnAc(2) in mobile phase. Samples were deproteinized by addition of equal volume of 0.6 mol/L HClO(4). Analytes in supernatants were separated by an Agilent HC-C18 (2) analytical column; an aqueous mobile phase containing 20 mmol/L NaAc, 3 mmol/L ZnAc(2) and 7% acetonitrile at flow rate of 1.0 mL/min. Detections were performed by a variable wavelength detector at wavelength 365 nm for KYN and a fluorescence detector at wavelengths excitation 344 nm and emission 398 nm for KYNA and TRP. Good linear responses were found with r(2)>0.999 for all analytes within the concentration range of physiological levels. The limit of detection of the developed method was 0.03 micromol/L, 0.9 nmol/L and 0.4 micromol/L for KYN, KYNA and TRP respectively. Recoveries from spiked human plasma were 95.4-99.7% for KYN, 98.9-104% for KYNA and 96.5-100.2% for TRP. All CVs for the repeatability and intermediate precision were less than 5%. We conclude that the developed method is helpful for the research investigations in KYN pathway of TRP metabolism.

Superiority of nitric acid for deproteinization in the determination of trace lithium in serum by graphite furnace atomic absorption spectrometry.

Physiological level of trace lithium in human serum was determined by graphite furnace atomic absorption spectrometry (GFAAS). 3.5% HNO3 (v/v) was employed as a protein precipitant for sample treatment and at the same time verified as a very effective chemical modifier to eliminate the interference of chloride. The analytical conditions for lithium determination in serum were investigated and the optimal pyrolysis and atomization temperatures were 800 degrees C and 2700 degrees C. The accuracy and precision of the method were tested by determining lithium in a RANDOX HN1530 assayed human multi-sera and a pooled human serum. The result was in good agreement with the target value and CV of the pooled human serum was 4.74% (n=10). The characteristic mass, the limit of detection (LOD) of the proposed method were 0.8 pg and 0.01 micromol/L, respectively. Median+/-S.E.M. of serum lithium in 220 Chinese people was 0.25+/-0.02 micromol/L.

Determination of trace lithium in human urine by electrothermal atomic absorption spectrometry using nitric acid as a chemical modifier to eliminate the interference of chloride.

Electrothermal atomic absorption spectrometry (ETAAS) is considered the most common and advanced technique to determine trace lithium in biological fluids. However, chloride existing in samples has been reported to create serious interferences. Nitric acid was verified as a chemical modifier to eliminate the interference of chloride in determining trace lithium in urine samples and the possible mechanism was also elucidated. The influence of chloride was completely eliminated by using 0.5% (v/v) HNO(3) as a chemical modifier. Confidence interval analysis on the difference for the slopes of linear regression curves indicated no significant difference between the slopes of aqueous and of urine-matched standard curves with and without 30 mmol/L NaCl in the presence of 0.5% (v/v) HNO(3) (P = 0.146). Thus the direct standardization with an aqueous calibration curve could be used instead of the standard-addition method. We conclude that the developed method is accurate and easily applicable for both routine use and research investigations.

In vitro glutaminase regulation and mechanisms of glutamate generation in HIV-1-infected macrophage.

Mononuclear phagocyte (MP, macrophages and microglia) dysfunction plays a significant role in the pathogenesis of HIV-1-associated dementia (HAD) through the production and release of soluble neurotoxic factors including glutamate. Glutamate production is greatly increased following HIV-1 infection of cultured MP, a process dependent upon the glutamate-generating enzyme glutaminase. Glutaminase inhibition was previously found to significantly decrease macrophage-mediated neurotoxicity. Potential mechanisms of glutaminase-mediated excitotoxicity including enzyme up-regulation, increased enzyme activity and glutaminase localization were investigated in this report. RNA and protein analysis of HIV-infected human primary macrophage revealed up-regulation of the glutaminase isoform GAC, yet identified no changes in the kidney-type glutaminase isoform over the course of infection. Glutaminase is a mitochondrial protein, but was found to be released into the cytosol and extracellular space following infection. This released enzyme is capable of rapidly converting the abundant extracellular amino acid glutamine into excitotoxic levels of glutamate in an energetically favorable process. These findings support glutaminase as a potential component of the HAD pathogenic process and identify a possible therapeutic avenue for the treatment of neuroinflammatory states such as HAD.

HIV-infected macrophages mediate neuronal apoptosis through mitochondrial glutaminase.

A significant number of patients infected with human immunodeficiency virus-1 (HIV-1) suffer cognitive impairment ranging from mild to severe HIV-associated dementia (HAD), a result of neuronal degeneration in the basal ganglia, cerebral cortex and hippocampus. Mononuclear phagocyte dysfunction is thought to play an important role in the pathogenesis of HAD. Glutamate neurotoxicity is triggered primarily by massive Ca2+ influx arising from over-stimulation of the NMDA subtype of glutamate receptors. The underlying mechanisms, however, remain elusive. We have tested the hypothesis that mitochondrial glutaminase in HIV-infected macrophages is involved in converting glutamine to glutamate. Our results demonstrate that the concentration of glutamate in HIV-1 infected conditioned media was dependent on glutamine dose, and HIV-1 infected conditioned medium mediated glutamine-dependent neurotoxicity. These results indicate HIV-infection mediates neurotoxicity through glutamate production. In addition, glutamate-mediated neurotoxicity correlated with caspase activation and neuronal cell cycle re-activation. Inhibition of mitochondrial glutaminase diminished the HIV-induced glutamate production, and attenuated NMDA over-stimulation and subsequent neuronal apoptosis. These data implicate mitochondrial glutaminase in the induction of glutamate-mediated neuronal apoptosis during HIV-associated dementia, and provides a possible therapeutic strategy for HAD treatment.

Glutamate production by HIV-1 infected human macrophage is blocked by the inhibition of glutaminase.

Mononuclear phagocyte (macrophages and microglia) dysfunction plays a significant role in the pathogenesis of human immunodeficiency virus (HIV) associated dementia (HAD) through the production and release of soluble neurotoxic factors including glutamate. The mechanism of glutamate regulation by HIV-1 infection remains unclear. In this report, we investigated whether the enzyme glutaminase is responsible for glutamate generation by HIV-1 infected monocyte-derived macrophages. We tested the functionality of novel small molecule inhibitors designed to specifically block the activity of glutaminase. Glutaminase inhibitors were first characterized in a kinetic assay with crude glutaminase from rat brain revealing an uncompetitive mechanism of inhibition. The inhibitors were then tested in vitro for their ability to prevent glutamate generation by HIV-infected macrophages, their effect upon macrophage viability, and HIV infection. To validate these findings, glutaminase specific siRNA was tested for its ability to prevent glutamate increase during infection. Our results show that both glutaminase specific small molecule inhibitors and glutaminase specific siRNA were effective at preventing increases in glutamate by HIV-1 infected macrophage. These findings support glutaminase as a potential component of the HAD pathogenic process and identify a possible therapeutic avenue for the treatment of neuroinflammatory states such as HAD.

PIN silicon diode fast neutron detector.

Two batches of diodes, with different structural ratios (the ratio of area and thickness), were made using different manufacturing processes. The energy response of the first batch to 15 kinds of monoenergetic neutrons ranging from 180 keV to 17.56 MeV was tested, and the neutron source response of both batches to 239Pu-Be neutron source was measured. The energy deposition in the diodes irradiated by 1 keV to 20 MeV monoenergetic neutrons was calculated with simulation procedure. The response curve of the experimental results showed an approximately similar trend to that of theoretical computation. Based on the results of the neutron source response experiments, it was concluded that the response of fast neutron varied linearly with the structural ratio of the detectors.