SPA-STOCSY: an automated tool for identifying annotated and non-annotated metabolites in high-throughput NMR spectra.

MOTIVATION: Nuclear magnetic resonance spectroscopy (NMR) is widely used to analyze metabolites in biological samples, but the analysis requires specific expertise, it is time-consuming, and can be inaccurate. Here, we present a powerful automate tool, SPatial clustering Algorithm-Statistical TOtal Correlation SpectroscopY (SPA-STOCSY), which overcomes challenges faced when analyzing NMR data and identifies metabolites in a sample with high accuracy. RESULTS: As a data-driven method, SPA-STOCSY estimates all parameters from the input dataset. It first investigates the covariance pattern among datapoints and then calculates the optimal threshold with which to cluster datapoints belonging to the same structural unit, i.e. the metabolite. Generated clusters are then automatically linked to a metabolite library to identify candidates. To assess SPA-STOCSY's efficiency and accuracy, we applied it to synthesized spectra and spectra acquired on Drosophila melanogaster tissue and human embryonic stem cells. In the synthesized spectra, SPA outperformed Statistical Recoupling of Variables (SRV), an existing method for clustering spectral peaks, by capturing a higher percentage of the signal regions and the close-to-zero noise regions. In the biological data, SPA-STOCSY performed comparably to the operator-based Chenomx analysis while avoiding operator bias, and it required <7 min of total computation time. Overall, SPA-STOCSY is a fast, accurate, and unbiased tool for untargeted analysis of metabolites in the NMR spectra. It may thus accelerate the use of NMR for scientific discoveries, medical diagnostics, and patient-specific decision making. AVAILABILITY AND IMPLEMENTATION: The codes of SPA-STOCSY are available at https://github.com/LiuzLab/SPA-STOCSY.

Functionalized Lanthanide(III) Complexes Constructed from Azobenzene Derivative and ß-Diketone Ligands: Luminescent, Magnetic, and Reversible Trans-to-Cis Photoisomerization Properties.

The coordination ability of ligands functionalized by azobenzene was manipulated, and two novel chelating ligands, (E)-4-(phenyldiazenyl)-N,N-bis(pyridin-2-ylmethyl) benzohydrazide (C25H22N6O, PBPM) and (E)-4-((4-(dimethylamino)phenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl) benzohydrazide (C27H27N7O, dmPBPM), were synthesized. The ligands can offer four coordinating atoms (one oxygen and three nitrogens) to act as tetradendate ligands, together with the two ß-diketonates (4,4,4-trifluoro-1-phenylbutane-1,3-dionate, tfd), and the trifluoroacetate anion presented as a ligand and a counterion to form the quaternary units with lanthanide(III) ions (La, Eu, and Gd), [Ln(tfd)2(PBPM)(CF3CO2)] (LnC47H34F9N6O7) and [Ln(tfd)2(dmPBPM)(CF3CO2)] (LnC49H39F9N7O7), where the lanthanide(III) ions are nine coordinated with N3O6 donor sets. All six complexes were structurally characterized, and four crystals were obtained and further analyzed by means of single-crystal X-ray diffraction. They all crystallized in the monoclinic P21/c space group with very similar lattice parameters, forming a monocapped twisted square antiprism. We successfully observed the photoluminescent properties of Eu(III) complexes at a wavelength of 614 nm in both solution and the solid state, as well as the trans-to-cis photoisomerization with the quantum yield (Φt→c = 10-2) of [Eu(tfd)2(PBPM)(CF3CO2)] complex that was comparable to that of PBPM. Moreover, the trans-to-cis photoisomerization rates of complexes [Ln(tfd)2(PBPM)(CF3CO2)] (La, Eu, Gd) (10-3-10-2 s -1) were also at the same level as that of PBPM and much higher than azobenzene itself (10-5-10-4 s-1). With the aid of TD-DFT calculations, the luminescence of Eu(III) complexes was found to originate from the attenuation effect of ß-diketonates. These features provide the foundation for the development of azobenzene-derived ß-diketonates lanthanide(III) complexes with photoisomerization and photoluminescence dual functions.

Ultrasensitive colorimetric assay of cadmium ion based on silver nanoparticles functionalized with 5-sulfosalicylic acid for wide practical applications.

Low-level cadmium ion (Cd(2+)) exposure contributes much toward the causation of chronic disease. Due to its low permissible exposure limit, overexposures may occur even in situations where trace quantities of Cd(2+) exist. So far, no effective treatment for Cd(2+) toxicity has been reported. Prevention of further exposure is the most important step in management of patients suggestive of Cd(2+) intoxication. Development of sensors for Cd(2+) is of great interest to ensure early diagnosis and improve management. We propose here a simple, low-cost (0.1$ per sample) yet very sensitive (limit of detection is 3.0 nM) and selective colorimetric assay for rapid (2 min) determination of Cd(2+) based on 5-sulfosalicylic acid functionalized silver nanoparticles (SAA-AgNPs). This method shows excellent selectivity for Cd(2+) over the other 16 metal ions. It is also precise and highly reproducible in determining Cd(2+) in real samples such as tap water, milk, serum, and urine with recoveries ranging from 93 to 110%, indicating the wide practical application to samples suspected of Cd(2+) exposure.

NMRQNet: a deep learning approach for automatic identification and quantification of metabolites using Nuclear Magnetic Resonance (NMR) in human plasma samples.

Nuclear Magnetic Resonance is a powerful platform that reveals the metabolomics profiles within biofluids or tissues and contributes to personalized treatments in medical practice. However, data volume and complexity hinder the exploration of NMR spectra. Besides, the lack of fast and accurate computational tools that can handle the automatic identification and quantification of essential metabolites from NMR spectra also slows the wide application of these techniques in clinical. We present NMRQNet, a deep-learning-based pipeline for automatic identification and quantification of dominant metabolite candidates within human plasma samples. The estimated relative concentrations could be further applied in statistical analysis to extract the potential biomarkers. We evaluate our method on multiple plasma samples, including species from mice to humans, curated using three anticoagulants, covering healthy and patient conditions in neurological disorder disease, greatly expanding the metabolomics analytical space in plasma. NMRQNet accurately reconstructed the original spectra and obtained significantly better quantification results than the earlier computational methods. Besides, NMRQNet also proposed relevant metabolites biomarkers that could potentially explain the risk factors associated with the condition. NMRQNet, with improved prediction performance, highlights the limitations in the existing approaches and has shown strong application potential for future metabolomics disease studies using plasma samples.

Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation.

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether MECP2 mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing MECP2 mutations greatly impact the key role of astrocytes in regulating overall brain bioenergetics and that these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal maturation, astrocytes rely on neurons to induce their complex stellate morphology and transcriptional changes. While MECP2 mutations cause cell-intrinsic aberrations in the astrocyte transcriptional landscape, surprisingly, they do not affect the neuron-induced astrocyte gene expression. Notably, however, astrocytes are unable to develop complex mature morphology due to cell- and non-cell-autonomous aberrations caused by MECP2 mutations. Thus, MECP2 mutations critically impact key cellular and molecular features of human astrocytes and, hence, their ability to interact and support the structural and functional maturation of neurons.

SPA-STOCSY: An Automated Tool for Identification of Annotated and Non-Annotated Metabolites in High-Throughput NMR Spectra.

Nuclear Magnetic Resonance (NMR) spectroscopy is widely used to analyze metabolites in biological samples, but the analysis can be cumbersome and inaccurate. Here, we present a powerful automated tool, SPA-STOCSY (Spatial Clustering Algorithm - Statistical Total Correlation Spectroscopy), which overcomes the challenges by identifying metabolites in each sample with high accuracy. As a data-driven method, SPA-STOCSY estimates all parameters from the input dataset, first investigating the covariance pattern and then calculating the optimal threshold with which to cluster data points belonging to the same structural unit, i.e. metabolite. The generated clusters are then automatically linked to a compound library to identify candidates. To assess SPA-STOCSY’s efficiency and accuracy, we applied it to synthesized and real NMR data obtained from Drosophila melanogaster brains and human embryonic stem cells. In the synthesized spectra, SPA outperforms Statistical Recoupling of Variables, an existing method for clustering spectral peaks, by capturing a higher percentage of the signal regions and the close-to-zero noise regions. In the real spectra, SPA-STOCSY performs comparably to operator-based Chenomx analysis but avoids operator bias and performs the analyses in less than seven minutes of total computation time. Overall, SPA-STOCSY is a fast, accurate, and unbiased tool for untargeted analysis of metabolites in the NMR spectra. As such, it might accelerate the utilization of NMR for scientific discoveries, medical diagnostics, and patient-specific decision making.

Role of propionates in substrate binding to heme oxygenase from Neisseria meningitidis: a nuclear magnetic resonance study.

Heme oxygenase (HO) cleaves hemin into biliverdin, iron, and CO. For mammalian HOs, both native hemin propionates are required for substrate binding and activity. The HO from the pathogenic bacterium Neisseria meningitidis (NmHO) possesses a crystallographically undetected C-terminal fragment that by solution (1)H nuclear magnetic resonance (NMR) is found to fold and interact with the active site. One of the substrate propionates has been proposed to form a salt bridge to the C-terminus rather than to the conventional buried cationic side chain in other HOs. Moreover, the C-terminal dipeptide Arg208His209 cleaves spontaneously over ~24 h at a rate dependent on substituent size. Two-dimensional (1)H NMR of NmHO azide complexes with hemins with selectively deleted or rearranged propionates shows that all bind to NmHO with a structurally conserved active site as reflected in optical spectra and NMR nuclear Overhauser effect spectroscopy cross-peak and hyperfine shift patterns. In contrast to mammalian HOs, NmHO requires only a single propionate interacting with the buried terminus of Lys16 to exhibit full activity and tolerates the existence of a propionate at the exposed 8-position. The structure of the C-terminus is qualitatively retained upon deletion of the 7-propionate, but a dramatic change in the 7-propionate carboxylate (13)C chemical shift upon C-terminal cleavage confirms its role in the interaction with the C-terminus. The stronger hydrophobic contacts between pyrroles A and B with NmHO contribute more substantially to the substrate binding free energy than in mammalian HOs, "liberating" one propionate to stabilize the C-terminus. The functional implications of the C-terminus in product release are discussed.

Influence of substrate modification and C-terminal truncation on the active site structure of substrate-bound heme oxygenase from Neisseriae meningitidis. A 1H NMR study.

Heme oxygenase (HO), from the pathogenic bacterium N. meningitidis(NmHO), which secures host iron, shares many properties with mammalian HOs but also exhibits some key differences. The crystal structure appears more compact, and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature of substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in NmHO are probed by 2D (1)H NMR to reveal unique structural features controlling substrate orientation. The thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl → methyl → hydrogen substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly stronger orientational preference, reflecting much stronger and selective pyrrole-I/II interactions with the protein matrix, than in mammalian HOs. Thus, replacing bulky vinyls with hydrogens results in a 180° rotation of substrate about the α,γ-meso axis in the active site. A "collapse" of the substrate pocket as substrate size decreases is reflected in movement of helix-2 toward the substrate as indicated by significant and selective increased NOESY cross-peak intensity, increase in steric Fe-CN tilt reflected in the orientation of the major magnetic axis, and decrease in steric constraints controlling the rate of aromatic ring reorientation. The active site of NmHO appears "stressed" for native protohemin, and its "collapse" upon replacing vinyls by hydrogen leads to a factor ~10(2) increase in substrate affinity. Interaction of the C-terminus with the active site destabilizes the crystallographic protohemin orientation by ~0.7 kcal/mol, which is consistent with optimizing the His207-Asp27 H-bond. Implications of the active site "stress" for product release are discussed.

Incurable and refractory spinal cystic echinococcosis: A case report.

BACKGROUND: Although the incidence and cure rate of spinal hydatidosis are low, the recurrence rate of spinal hydatidosis is high, and the prognosis of spinal hydatidosis is poor. Therefore, we report a typical case of refractory spinal hydatidosis to increase spine surgeons' awareness of the disease and reduce misdiagnosis and recurrence. CASE SUMMARY: A 48-year-old man presented with back pain, significant weight loss, and paralysis of both lower limbs. The patient was misdiagnosed with spinal tuberculosis in an outside hospital. However, spinal magnetic resonance imaging (MRI) showed hyperintense cystic components on T2-weighted images and hypointensity on T1-weighted images. A lobulated, multiocular, honeycomb-appearance, septated cystic mass protruding intraspinally and compressing the spinal cord at segments T8-T9 was present. Paravertebral polycystic lobular lesions presented as a "bunch of grapes". The ELISA test result for Echinococcus granulosus was positive. Then, a diagnosis of spinal hydatidosis and lung hydatid disease was made, and the patient underwent left transthoracic approach lobectomy, paravertebral lesion debridement, and subtotal vertebrectomy with vertebral body replacement of segments T8 and T9 by a mesh cage. The patient also underwent albendazole chemotherapy before and after surgery. One year after stopping the drug therapy, the patient developed recurrent T5 vertebral lesions and underwent a second subtotal vertebrectomy surgery. The patient is currently in good condition and is receiving long-term medication and follow-up. CONCLUSION: The MRI feature of a "bunch of grapes" is a typical imaging indication of spinal hydatidosis. Subtotal vertebrectomy is a risk factor for postoperative recurrence. Total spondylectomy makes it possible to cure spinal hydatidosis, but antiparasitic drug therapy is also an important supplementary therapy to multimodal therapy. It is preferable for patients with spinal hydatidosis to receive life-long antiparasitic medication therapy and follow-up.

1H NMR study of the influence of mutation on the interaction of the C-terminus with the active site in heme oxygenase from Neisseria meningitidis: implications for product release.

The HO from the pathogenic bacterium Neisseria meningitidis, NmHO, possesses C-terminal His207, Arg208, and His209 residues that are undetected in crystal structures. NMR found the C-terminus ordered and interacting with the active site and shown to undergo a spontaneous cleavage of the C-terminal Arg208-His209 bond that affects the product off rate. A preliminary model for the interaction based on the wild-type (WT) NmHO complexes has been presented [Liu, Y., Ma, L.-H., Satterlee, J. D., Zhang, X., Yoshida, T., and La Mar, G. N. (2006) Biochemistry 45, 3875-3886]. Two-dimensional (1)H NMR data of resting-state, azide-inhibited substrate complexes of the three C-terminal truncation mutants (Des-His209-, Des-Arg208His209-, and Des-His207Arg208His209-NmHO) confirm the previous proposed roles for His207 and Arg208 and reveal important additional salt bridges involving the His209 carboxylate and the side chains of both Lys126 and Arg208. Deletion of His209 leads to a qualitatively retained C-terminal geometry, but with increased separation between the C-terminus and active site. Moreover, replacing vinyls with methyls on the substrate leads to a decrease in the separation between the C-terminus and the active site. The expanded model for the C-terminus reveals a less stable His207-Arg208 cis peptide bond, providing a rationalization for its spontaneous cleavage. The rate of this spontaneous cleavage is shown to correlate with the proximity of the C-terminus to the active site, suggesting that the closer interaction leads to increased strain on the already weak His207-Arg208 peptide bond. The relevance of the C-terminus structure for in vitro studies, and the physiological function of product release, is discussed.

The role of active site residues in the oxidant specificity of the Orp1 thiol peroxidase.

In this study we investigated the role of active site residues in the peroxidase activity of Orp1 (GPx3) using three different peroxide substrates. Using a structural homology model of the reduced form of Orp1, we identified Asn126 and Phe127 as evolutionarily conserved residues that line the back of the Orp1 active site and which are likely to affect the peroxidase activity of Orp1. Additionally, we identified Phe38 as a surface residue that could influence substrate specificity as it is located adjacent to Cys36, in the same position occupied by similar hydrophobic amino acids in many Orp1 homologs. We individually mutated these residues to alanine and examined the effect of each mutation in vitro and in vivo. Chloro-4-nitrobenzo-2-oxa-1,3-diazole was used to identify Cys-SOH modification of Cys36 in response to H(2)O(2), tert-butyl-hydroperoxide (tert-BHP), and cumene hydroperoxide (CHP) in Orp1(WT). Mutation of Asn126 and Phe127 eliminate Cys-SOH formation and peroxidase activity in response to H(2)O(2), tert-BHP and CHP. Furthermore, the pK(a) of Cys36 is elevated closer to that of free cysteine compared to Orp1(WT). Mutation of Phe38 does not affect the peroxidase activity of Orp1 upon exposure to H(2)O(2). The Phe38 mutation decreases Orp1 peroxidase activities in response to either tert-BHP or CHP. The in vivo sensitivity of the Phe38 mutant to both tert-BHP and CHP is increased, while the H(2)O(2) sensitivity is unchanged. The pK(a) of Cys36 in the Phe38 mutant is 5.0, which is the same as Orp1(WT). Taken together, these results suggest that Phe38 does not play a role in the reactivity of Cys36, but does modulate the affinity of Orp1 for alkyl hydroperoxides.

Coupling of the distal hydrogen bond network to the exogenous ligand in substrate-bound, resting state human heme oxygenase.

Mammalian heme oxygenase (HO) possesses catalytically implicated distal ordered water molecules within an extended H-bond network, with one of the ordered water molecules (#1) providing a bridge between the iron-coordinated ligand and the catalytically critical Asp140, that, in turn, serves as an acceptor for the Tyr58 OH H-bond. The degree of H-bonding by the ligated water molecule and the coupling of this water molecule to the H-bond network are of current interest and are herein investigated by (1)H NMR. Two-dimensional NMR allowed sufficient assignments to provide both the H-bond strength and hyperfine shifts, the latter of which were used to quantify the magnetic anisotropy in both the ferric high-spin aquo and low-spin hydroxo complexes. The anisotropy in the aquo complex indicates that the H-bond donation to water #1 is marginally stronger than in a bacterial HO, while the anisotropy for the hydroxo complex reveals a conventional (d(xz), d(yz))(1) ground state indicative of only moderate to weak H-bond acceptance by the ligated hydroxide. Mapping out the changes of the H-bond strengths in the network during the ligated water --> hydroxide conversion by correcting for the effects of magnetic anisotropy reveals a very substantial change in H-bond strength for Tyr58 OH and lesser effects on nearby H-bonds. The effect of pH on the H-bonding network in human HO is much larger and transmitted much further from the iron than in a pathogenic bacterial HO. The implications for the HO mechanism of the H-bond of Tyr58 to Asp140 are discussed.

[Study on antidepressant components of sucrose ester from Polygala tenuifolia].

OBJECTIVE: To investigate the antidepressant components of Polygala tenuifolia. METHOD: The chromatographic method was used to isolate and purify the chemical constituents, their structures were identified by spectral analysis, MTT method was applied to investigate their cytotoxic activities. RESULT: Nine compounds were isolated from the roots of P. tenuifolia. Their structures were identified as sibiricose A, (1), sibiricose A5 (2), tenuifoliside A (3) and 3', 6-disinapoyl sucrose (4), sibiricose A6 (5), 3, 4, 5-trimethoxycinnamate (6), polygalaxanthone III (7), tenuifolioses A (8), tenuifolioses H (9) and some compounds' activities to PC12 were observed. CONCLUSION: Compound 1 was isolated from this plant for the first time. Compounds 2,3 could protect PC12 cells damage induced by P. tenuifolia.

Near-Infrared Photoluminescence and Reversible Trans-to-Cis Photoisomerization of Mononuclear and Binuclear Ytterbium(III) Complexes Functionalized by Azobenzene Groups.

Two mononuclear and one binuclear ytterbium complexes with dual near-infrared (NIR) photoluminescence and reversible trans-to-cis photoisomerization functions were synthesized and characterized. The central ytterbium(III) ion coordinates with two ß-diketonate (4,4,4-trifluoro-1-phenylbutane-1,3-dionate (tfd)) ligands and one deprotonated azobenzene-containing tetradentate ligand [(E)-4-(phenyldiazenyl)-N,N-bis(pyridin-2-ylmethyl) benzohydrazide (HL), (E)-4-((4-(dimethylamino)phenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)benzohydrazide (HNL), or (E)-4,4'-N',N'-bis(pyridin-2-ylmethyl)benzohydrazide azobenzene (H2DL)] to form a neutral ternary complex ([Yb(tfd)2L], [Yb(tfd)2(NL)], or [Yb2(tfd)4(DL)], respectively), where the ytterbium(III) ion is eight-coordinated to N3O5 donor sets. X-ray crystallographic analysis shows that all three complexes form a trigonal dodecahedron geometry with similar -N=N- distances that are slightly longer than those of the pure azobenzene-containing ligands. The NIR luminescence properties of the Yb(III) complexes were determined at a wavelength of about 980 nm with quantum yields in the range of 0.4-0.6% in ethanol and acetonitrile solutions at room temperature, and trans-to-cis photoisomerization was determined with the quantum yields (Φt→c = 10-2) at the same level as their pure ligands. The trans-to-cis photoisomerization rates of the complexes (10-4 s-1) are slightly higher than those of the pure ligands and similar to azobenzene (10-5 to 10-4 s-1). From time-dependent density functional theory calculations of the energy levels of the first excited triplet states of the ligands, the energies of the lowest excited triplet states of all of the ligands are higher than the resonance level of Yb3+ (2F5/2, 1.2722 eV). We suggest that these azo-containing ligands may participate in energy transfer to the ytterbium ion, in addition to the main "antenna effect" ligand tfd. This is the first report of azobenzene group-functionalized ytterbium complexes with dual NIR luminescence and photoisomerization properties, indicating that azobenzene-containing lanthanide(III) complexes have potential applications as dual function materials in biological systems.

Azobenzene-derived tris-ß-diketonate lanthanide complexes: reversible trans-to-cis photoisomerization in solution and solid state.

Novel azobenzene-derived ß-diketonates (4,4,5,5,6,6,6-heptafluoro-1-azobenzene-1,3-hexanedione (LA), 4,4,5,5,6,6,6-heptafluoro-1-(4-dimethylamino)azobenzene-1,3-hexanedione (LB)) were designed and their complexes with lanthanide cations (La(3+), Eu(3+), Gd(3+), Yb(3+)) were prepared and characterized by (1)H NMR, FT-IR, and elemental analysis. Three of the complexes were crystallized successfully and identified by X-ray diffraction. It was significant to find that LA showed remarkably reversible trans-to-cis isomerization properties, however, LB, bearing an electron donor compared with LA, slowed down the isomerization to an extent. The presence of Ln(iii) enhanced the reversible trans-to-cis isomerization properties of both LA and LB a little upon photoirradiation in organic solvents, and amazingly increased the fatigue resistance. In addition, the complexes doped in polymethyl methacrylate (PMMA) films produced a similar phenomenon as well as when in solution. Theoretical calculations based on time dependent density functional theory (TD-DFT) were performed for geometry optimization and to determine the excitation energies of LA and LB to gain further insight into the electronic structure of the complexes, and the data were consistent with the experimental results. The excellent reversible photoisomerization properties of the newly designed Ln(iii) complexes can offer important advantages that will help with the further study of these materials to reach their full potential in applications such as molecular switching devices.

Intraperitoneal Injection of Multiplacentas Pooled Cells Treatment on a Mouse Model with Aplastic Anemia.

Coinfusion of hematopoietic and mesenchymal stem cells is more effective than hematopoietic stem cell transplantation alone. It is necessary to explore a safe and routine mixed stem cell intraperitoneal transplantation method. Multiplacentas pooled cells were intraperitoneally injected into a radiation- and immunity-induced mouse aplastic anemia model with single time. Then, mouse survival time, peripheral blood hemoglobin count, bone marrow architecture, and donor cell engraftment were assessed. The recipient mouse exhibited donor cell engraftment in both bone marrow and peripheral blood. Survival time and peripheral blood hemoglobin count increased in placenta pooled cells treated mice, compared with model-only controls (P = 0.048 and P = 0.000, resp.). However, placentas pooled cells failed to cause a significant decrease in bone marrow pimelosis area (P = 0.357). Intraperitoneally transplanted multiplacentas pooled cells can survive and engraft into a host body through blood circulation, which can increase the life span of an aplastic anemia model mice, and delay but not abrogate the development of aplastic anemia. Furthermore, they appear to play a role in increasing peripheral blood hemoglobin level response for increasing the life span of aplastic anemia model mice.

Characteristics of participants' and caregivers' influence on non-response in a cross-sectional study of dementia in an older population.

OBJECTIVE: The issue of non-response in dementia epidemiological studies, which may result in the underestimation of the prevalence of dementia, has attracted little attention. We aimed to explore the causes and related factors of non-response in a dementia survey among Chinese veterans. METHODS: A two-phase, cross-sectional study investigated the prevalence of dementia and mild cognitive impairment in Chinese veterans aged ≥ 60 years. We collected the socio-demographic data and prior medical history, evaluated the health status of veterans and their caregivers, assessed the cognitive status of veterans, and evaluated the care burden of caregivers by Caregiver Burden Inventory (CBI). RESULTS: Of 9676 eligible participants, 525 (5.4%) veterans in phase 1 and 1706 (35.0%) veterans among 4875 veterans in phase 2 did not respond. Illness, hospitalization and death accounted for 63.0% and 75.5% non-response in phases 1 and 2, respectively. Non-participation in social activities, self-perceived poor health status, worsened health changes, self-reported need for life care, and history of hearing loss or glaucoma independently predicted non-response in phase 1 or 2. The heavy care burden, suggested by the higher CBI scores and self-reported health deterioration of the primary caregivers, predicted non-response in phase 1 or 2. CONCLUSIONS: The negative factors from both the participants and their caregivers independently predicted the non-response in the dementia study in an older population. Preventative strategies from the perspectives of the participants and caregivers should be developed to improve the response rates in both phases in a cross-sectional study.

Ultrasensitive turn-on fluorescent detection of trace thiocyanate based on fluorescence resonance energy transfer.

Thiocyanate (SCN(-)) is a small anion byproduct of cyanide metabolism. Several methods have been reported to measure SCN(-) above the micromolar level. However, SCN(-) is derived from many sources such as cigarettes, waste water, food and even car exhaust and its effect is cumulative, which makes it necessary to develop methods for the detection of trace SCN(-). In this paper, a simple and ultrasensitive turn-on fluorescence assay of trace SCN(-) is established based on the fluorescence resonance energy transfer (FRET) between gold nanoparticles (AuNPs) and fluorescein. The detection limit is 0.09 nM, to the best of our knowledge, which has been the lowest detection LOD ever without the aid of costly instrumentation. The fluorescence of fluorescein is significantly quenched when it is attached to the surface of AuNPs. Upon the addition of SCN(-), the fluorescence is turned on due to the competition action between SCN(-) and fluorescein towards the surface of AuNPs. Under an optimum pH, AuNPs size and concentration, incubation time, the fluorescence enhancement efficiency [(IF-I0)/I0] displays a linear relationship with the concentration of SCN(-) in the range of 1.0 nM to 40.0 nM. The fluorescein-AuNP sensor shows absolutely high selectivity toward SCN(-) than other 16 anions. The common metal ions, amino acids and sugars have no obvious interference effects. The accuracy and precision were evaluated based on the recovery experiments. The cost effective sensing system is successfully applied for the determination of SCN(-) in milk products and saliva samples.

[Levels and distribution of organochlorine pesticides and dioxin-like polychlorinated biphenyls in atmospheric particulates in Xining and Tianjun, Qinghai province, China].

The levels of OCPs and DL-PCBs in the atmospheric particulates of Xining city and Tianjun county in Qinghai province were determined. DDTs and HCHs were the main component of OCPs in the atmospheric particulates. The average levels of DDTs and HCHs in the atmospheric particulates of Xining city were 35 pg x m(-3) and 5.9 pg x m(-3) in summer and 93 pg x m(-3) and 11 pg x m(-3) in winter, respectively. In Tianjun county, they were 83 pg x m(-3) and 6.4 pg x m(-3) in summer and 28 pg x m(-3) and 6.7 pg x m(-3) in winter, respectively. Compared with other Asian areas, the average levels of them in Qinghai province were lower. Meanwhile, the average levels of DL-PCBs in Xining city were 0.52 pg x m(-3) in summer and 0.99 pg x m(-3) in winter, respectively, and in Tianjun county were 0.58 pg x m(-3) in summer and 0.52 pg x m(-3) in winter, respectively. The average levels of OCPs in summer and winter of Xining city were higher than those in Tianjun county, but the average levels of DL-PCBs in two cities were similar. Compared with the polar region, the distribution principles of DL-PCBs in the plateau area were certainly similar, while HCHs and DDTs were different.

Proteomic analysis of adverse outcomes in patients with acute coronary syndromes.

BACKGROUND: Most biomarkers lack clinical sensitivity and specificity for predicting adverse outcomes in patients with acute coronary syndromes (ACS). We identified potential predictors through proteomic analysis. METHODS: Serum proteomic analysis was performed by surface-enhanced laser desorption/ionization protein chip technology in 409 patients with ACS. The primary endpoints were 30-day and 3-year occurrence of major adverse cardiovascular events (cardiac death, non-fatal myocardial infarction and target lesion revascularization). RESULTS: A m/z 4174.39 peak was associated with an increased incidence of 3-year events. In multivariate analysis, the m/z 4174.39 peak showed an independent correlation with 3-year (over 30-day) events (hazard ratio, 2.33; 95% confidence interval (CI), 1.23 to 4.39; P=0.009 for the fourth versus first quartile), while the creatine kinase MB fraction (CK-MB) and troponin T levels were associated with 30-day events ((ln CK-MB: hazard ratio, 1.36; 95% CI, 1.07 to 1.73; P=0.013); (ln troponin T: hazard ratio, 1.36; 95% CI, 1.12 to 1.64; P=0.002)). CONCLUSIONS: The m/z 4174.39 peak is a strong marker for predicting the long-term outcomes, and may correspond to a new biomarker, such as a member of the CXC chemokine family, and provide additional prognostic value in ACS.