706 research outputs found
Partition of a Binary Matrix into k
A biclustering problem consists of objects and an attribute vector for each object. Biclustering aims at finding a bicluster—a subset of objects that exhibit similar behavior across a subset of attributes, or vice versa. Biclustering in matrices with binary entries (“0”/“1”) can be simplified into the problem of finding submatrices with entries of “1.” In this paper, we consider a variant of the biclustering problem: the k-submatrix partition of binary matrices problem. The input of the problem contains an n×m matrix with entries (“0”/“1”) and a constant positive integer k. The k-submatrix partition of binary matrices problem is to find exactly k submatrices with entries of “1” such that these k submatrices are pairwise row and column exclusive and each row (column) in the matrix occurs in exactly one of the k submatrices. We discuss the complexity of the k-submatrix partition of binary matrices problem and show that the problem is NP-hard for any k≥3 by reduction from a biclustering problem in bipartite graphs
Proteomic Analysis of the Effect of Fuzheng Huayu Recipe on Fibrotic Liver in Rats
Hepatic fibrosis is a common pathological process of chronic liver diseases and would lead to cirrhosis, and Fuzheng Huayu (FZHY) is an effective Chinese herbal product against liver fibrosis. This study observes FZHY influence on proteome of fibrotic liver with differential proteomic approach and aims to understand FZHY multiple action mechanisms on liver fibrosis.
The liver fibrosis models were induced with intraperitoneal injection of dimethylnitrosamine for 4 weeks in rats and divided into model control (model) and FZHY-treated (FZHY) groups, while normal rats were used as normal control (normal). After model establishment, rats in FZHY groups were administered 4 g/kg wt of FZHY for 4 weeks, and normal and model groups were given the same volume of saline. The liver proteins in the above 3 groups were separated by two-dimensional gel electrophoresis (2-DE), the differentially expressed spots were analyzed and compared between normal and model or model and FZHY groups, and then the proteins were identified with mass spectrum analysis and validated partially with western blot and real-time PCR. 1000~1200 spots were displayed on each 2D gel, and a total of 61 protein spots were found with significant intensity difference between normal control or FZHY and model control. 23 most obviously differential spots were excised, and in-gel digestion and 21 peptide mass fingerprints (PMF) were obtained with MALDI-TOF MS analysis, and 14 proteins were identified through protein database searching. Among 14 differentially expressed proteins, 8 proteins in normal and FZHY groups had the same tendency of differential expression compared with the ones in model group. And one of them, vimentin, was validated by western blot and real-time PCR analyses. Our study reveals 12 proteins responsible for fibrogenesis induced by DMN in rats, and among them, 8 proteins in fibrotic liver were regulated by FZHY, including aldehyde dehydrogenase, vimentin isoform (CRA_b), gamma-actin, vimentin, fructose-bisphosphate aldolase B, aldo-keto reductase, S-adenosylhomocysteine hydrolase isoform, and HSP90. It indicates that the action mechanism of FZHY antiliver fibrosis may be associated with modulation of proteins associated with metabolism and stress response, as well as myofibroblast activation. The study provides new insights and data for exploring the liver fibrogenesis pathophysiology and FZHY action mechanism against liver fibrosis
The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS
Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation
Bridging multiscale interfaces for developing ionically conductive high-voltage iron sulfate-containing sodium-based battery positive electrodes
Non-aqueous sodium-ion batteries (SiBs) are a viable electrochemical energy storage system for grid storage. However, the practical development of SiBs is hindered mainly by the sluggish kinetics and interfacial instability of positive-electrode active materials, such as polyanion-type iron-based sulfates, at high voltage. Here, to circumvent these issues, we proposed the multiscale interface engineering of NaFe(SO), where bulk heterostructure and exposed crystal plane were tuned to improve the Na-ion storage performance. Physicochemical characterizations and theoretical calculations suggested that the heterostructure of NaFe(SO) phase facilitated ionic kinetics by densifying Na-ion migration channels and lowering energy barriers. The (11-2) plane of NaFe(SO) promoted the adsorption of the electrolyte solution ClO4− anions and fluoroethylene carbonate molecules, which formed an inorganic-rich Na-ion conductive interphase at the positive electrode. When tested in combination with a presodiated FeS/carbon-based negative electrode in laboratory- scale single-layer pouch cell configuration, the NaFe(SO)-based positive electrode enables an initial discharge capacity of about 83.9 mAh g, an average cell discharge voltage of 2.35 V and a specific capacity retention of around 97% after 40 cycles at 24 mA g and 25 °C
Intrathoracic Endotracheal Metastasis from Nasopharyngeal Carcinoma: A First Case Report and Review of the Literature
Intrathoracic endotracheal metastasis from a very distant site is extremely rare. We report the first case of such a disease in a 68-year-old man with nasopharyngeal carcinoma who presented with a cough and hemoptysis 34 months after finishing radiotherapy. Prior to tracheal metastasis, he developed a solitary metastasis in the lung and underwent chemotherapy followed by radiotherapy. Computed tomography showed the presence of an enlarged lymph node in the para-aortic arch. Fiberoptic bronchoscopy revealed an endotracheal tumor 1 cm above the carina. Histological and immunohistochemical analyses confirmed its nasopharyngeal origin. He was treated with conventional radiotherapy and three-dimensional conformal radiotherapy; complete tumor remission was achieved. He died of nonmalignant disease with no signs of tumor recurrence 2 years after treatment completion. Radiotherapy may be an appropriate management approach to achieve long-term tumor control for this disease
Reduced SV2A and GABA receptor levels in the brains of type 2 diabetic rats revealed by [F]SDM-8 and [F]flumazenil PET
PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer's disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2 A (SV2A), γ-aminobutyric acid type A (GABA) receptor, amyloid-β, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats.
Methods: Positron emission tomography (PET) using [F]SDM-8 (SV2A), [F]flumazenil (GABA receptor), [F]florbetapir (amyloid-β), [F]PM-PBB3 (tau), and [F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and SpragueDawley (SD) rats. Immunofluorescence staining, Thioflavin S staining, proteomic profiling and pathway analysis were performed on the brain tissues of ZDF and SD rats.
Results: Reduced cortical [F]SDM-8 uptake and cortical and hippocampal [F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. The regional uptake of [F]florbetapir and [F]PM-PBB3 was comparable in the brains of 12-month-old ZDF and SD rats. Immunofluorescence staining revealed Thioflavin S-negative, phospho-tau-positive inclusions in the cortex and hypothalamus in the brains of ZDF rats and the absence of amyloid-beta deposits. The level of GABA receptors was lower in the cortex of ZDF rats than SD rats. Proteomic analysis further demonstrated that, compared with SD rats, synaptic-related proteins and pathways were downregulated in the hippocampus of ZDF rats.
Conclusion: These findings provide in vivo evidence for regional reductions in SV2A and GABA receptor levels in the brains of aged T2DM ZDF rats
In vivo reactive astrocyte imaging using 18FSMBT-1 in tauopathy and familial Alzheimer’s disease mouse models: A multi-tracer study
Background: Reactive astrocytes play an important role in the development of Alzheimer's disease and primary tauopathies. Here, we aimed to investigate the relationships between reactive astrocytes. Microgliosis and glucose metabolism with Tau and amyloid beta pathology by using multi-tracer imaging in widely used tauopathy and familial Alzheimer's disease mouse models.
Results: Positron emission tomography imaging using 18FPM-PBB3 (tau), 18Fflorbetapir (amyloid-beta), 18FSMBT-1 (monoamine oxidase-B), 18FDPA-714 (translocator protein) and 18Ffluorodeoxyglucose was carried out in 3- and 7-month-old rTg4510 tau mice, 5 × FAD familial Alzheimer's disease mice and wild-type mice. Immunofluorescence staining was performed to validate the pathological distribution in the mouse brain after in vivo imaging. We found increased regional levels of 18FPM-PBB3, 18FSMBT-1, and 18FDPA-714 and hypoglucose metabolism in the brains of 7-month-old rTg4510 mice compared to age-matched wild-type mice. Increased 18FSMBT-1 uptake was observed in the brains of 3, 7-month-old 5 × FAD mice, with elevated regional 18Fflorbetapir and 18FDPA-714 uptakes in the brains of 7-month-old 5 × FAD mice, compared to age-matched wild-type mice. Positive correlations were shown between 18FSMBT-1 and 18FPM-PBB3, 18FDPA-714 and 18FPM-PBB3 in rTg4510 mice, and between 18Fflorbetapir and 18FDPA-714 SUVRs in 5 × FAD mice.
Conclusion: In summary, these findings provide in vivo evidence that reactive astrocytes, microglial activation, and cerebral hypoglucose metabolism are associated with tau and amyloid pathology development in animal models of tauopathy and familial Alzheimer's disease
Association Between Polymorphisms in Estrogen Receptor Genes and Depression in Women: A Meta-Analysis
Objective: It is suggested that estrogen receptors (ERs) might be associated with the disproportionate vulnerability of women to depressive episodes. Several variants in ER-alpha (ERα) and ER-beta (ERβ) have been linked to depression, but the results were not consistent. Hence, we conducted a meta-analysis to evaluate the association between ERα/ERβ and depression in a cohort of women.Methods: A comprehensive literature search was performed in public databases. The genetic association between polymorphisms in Erα/ERβ and depression risk in a cohort of women was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Cochran’s Q test and the I2 index were used to evaluate heterogeneity.Results: In total, 10 studies and 4 SNPs (rs2234693, rs9340799, rs4986938, rs1256049) were included in our meta-analysis. rs2234693 genotype was significantly associated with the risk of depression in women by dominant model (CC + CT vs TT, OR = 1.30, 95% CI: 1.09–1.55, p = 0.0031), recessive model (CC vs CT + TT, OR = 1.64, 95% CI: 1.00–2.67, p = 0.0478), additive model (CC vs TT, OR = 1.93, 95% CI: 1.12–3.35, p = 0.0189) and allelic model (C vs T, OR = 1.24, 95% CI: 1.10–1.39, p = 0.0003). For rs9340799, the frequencies of risk genotypes according to the dominant (GG + GA vs AA, OR = 1.47, 95% CI = 1.10–1.98, p = 0.0096, I2 = 0%, p = 0.43) and allelic (G vs A, OR = 1.33, 95% CI: 1.04–1.69, p = 0.0236, I2 = 0%, p = 0.39) models were significantly lower in women with depression than in controls within the Asian subgroup. For rs1256049, risk genotypes were significantly more frequent in depressed subjects than in controls under the dominant model (AA+ GA vs GG, OR = 1.62, 95% CI: 1.19–2.21, p = 0.0024) and the allelic model (A vs G, OR = 1.35, 95% CI: 1.07–1.72, p = 0.012) after sensitivity analysis by omitting one study which induce the heterogeneity.Conclusions: The current meta-analysis is the first and most comprehensive investigation of the association between ERs and depression in women, and the findings support the concept that ERs participate in the etiology of sex heterogeneity in depression
A Novel Method for Evaluating the Cardiotoxicity of Traditional Chinese Medicine Compatibility by Using Support Vector Machine Model Combined with Metabonomics
Traditional biochemical and histopathological tests have been used to evaluate the safety of traditional Chinese medicine (TCM) compatibility for a long time. But these methods lack high sensitivity and specificity. In the previous study, we have found ten biomarkers related to cardiotoxicity and established a support vector machine (SVM) prediction model. Results showed a good sensitivity and specificity. Therefore, in this study, we used SVM model combined with metabonomics UPLC/Q-TOF-MS technology to build a rapid and sensitivity and specificity method to predict the cardiotoxicity of TCM compatibility. This study firstly applied SVM model to the prediction of cardiotoxicity in TCM compatibility containing Aconiti Lateralis Radix Praeparata and further identified whether the cardiotoxicity increased after Aconiti Lateralis Radix Praeparata combined with other TCM. This study provides a new idea for studying the evaluation of the cardiotoxicity caused by compatibility of TCM
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