Galectin-3 aggravates microglial activation and tau transmission in tauopathy.

Alzheimer's disease is characterized by the accumulation of amyloid-ß plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a ß-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3-associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy.

The Utilization of Optically Induced Dielectrophoresis (ODEP)-Based Cell Manipulation in a Microfluidic System for the Purification and Sorting of Circulating Tumor Cells (CTCs) with Different Sizes.

The analysis of circulating tumor cells (CTCs) at the molecular level holds great promise for several clinical applications. For this goal, the harvest of high-purity, size-sorted CTCs with different subtypes from a blood sample are important. For this purpose, a two-step CTC isolation protocol was proposed, by which the immunomagnetic beads-based cell separation was first utilized to remove the majority of blood cells. After that, an optically induced dielectrophoresis (ODEP) microfluidic system was developed to (1) purify the CTCs from the remaining magnetic microbeads-bound blood cells and to (2) sort and separate the CTCs with different sizes. In this study, the ODEP microfluidic system was designed and fabricated. Moreover, its optimum operation conditions and performance were explored. The results exhibited that the presented technique was able to purify and sort the cancer cells with two different sizes from a tested cell suspension in a high-purity (93.5% and 90.1% for the OECM 1 and HA22T cancer cells, respectively) manner. Overall, this study presented a technique for the purification and sorting of cancer cells with different sizes. Apart from this application, the technique is also useful for other applications in which the high-purity and label-free purification and sorting of cells with different sizes is required.

Recent Progress in Enhanced Cancer Diagnosis, Prognosis, and Monitoring Using a Combined Analysis of the Number of Circulating Tumor Cells (CTCs) and Other Clinical Parameters.

Analysis of circulating tumor cells (CTCs) holds promise to diagnose cancer or monitor its development. Among the methods, counting CTC numbers in blood samples could be the simplest way to implement it. Nevertheless, its clinical utility has not yet been fully accepted. The reasons could be due to the rarity and heterogeneity of CTCs in blood samples that could lead to misleading results from assays only based on single CTC counts. To address this issue, a feasible direction is to combine the CTC counts with other clinical data for analysis. Recent studies have demonstrated the use of this new strategy for early detection and prognosis evaluation of cancers, or even for the distinguishment of cancers with different stages. Overall, this approach could pave a new path to improve the technical problems in the clinical applications of CTC counting techniques. In this review, the information relevant to CTCs, including their characteristics, clinical use of CTC counting, and technologies for CTC enrichment, were first introduced. This was followed by discussing the challenges and new perspectives of CTC counting techniques for clinical applications. Finally, the advantages and the recent progress in combining CTC counts with other clinical parameters for clinical applications have been discussed.

Anomaly Detection in Automatic Meter Intelligence System Using Positive Unlabeled Learning and Multiple Symbolic Aggregate Approximation.

With the development of automatic electrical devices in smart grids, the data generated by time and transmitted are vast and thus impossible to control consumption by humans. The problem of abnormal detection in power consumption is crucial in monitoring and controlling smart grids. This article proposes the detection of electrical meter anomalies by detecting abnormal patterns and learning unlabeled data. Furthermore, a framework for big data and machine learning-based anomaly detection framework are introduced. The experimental results show that the time series anomaly detection for electric meters has better results in accuracy and time than the expert alternatives.

Dataset on the effect of extracurricular activities on positive youth development.

This article present dataset that reflects the perception of extracurricular activities and positive development among youth at 12 schools in Vietnam. In addition, the dataset also explores the relationship between extracurricular activities and positive youth development in Vietnam context. The dataset was collected from adolescents living in three provinces in Vietnam, including: Ha Noi, Nam Dinh, Nghe An and took place in March 2021. The final dataset included 416 fulfilled responses and was used for quantitative analysis through three steps, including: test coefficient alpha, exploratory factors analysis; confirming factors analysis; structural equation modelling. The dataset was obtained as a reference source for future research on positive youth development.

Equilibrative nucleoside transporter 1 inhibition rescues energy dysfunction and pathology in a model of tauopathy.

Tau pathology is instrumental in the gradual loss of neuronal functions and cognitive decline in tauopathies, including Alzheimer's disease (AD). Earlier reports showed that adenosine metabolism is abnormal in the brain of AD patients while consequences remained ill-defined. Herein, we aimed at investigating whether manipulation of adenosine tone would impact Tau pathology, associated molecular alterations and subsequent neurodegeneration. We demonstrated that treatment with an inhibitor (J4) of equilibrative nucleoside transporter 1 (ENT1) exerted beneficial effects in a mouse model of Tauopathy. Treatment with J4 not only reduced Tau hyperphosphorylation but also rescued memory deficits, mitochondrial dysfunction, synaptic loss, and abnormal expression of immune-related gene signatures. These beneficial effects were particularly ascribed to the ability of J4 to suppress the overactivation of AMPK (an energy reduction sensor), suggesting that normalization of energy dysfunction mitigates neuronal dysfunctions in Tauopathy. Collectively, these data highlight that targeting adenosine metabolism is a novel strategy for tauopathies.

Correlation of magnetic and magnetoresistive properties of nanoporous Co/Pd thin multilayers fabricated on anodized TiO2 templates.

In this study, we consider a technological approach to obtain a high perpendicular magnetic anisotropy of the Co/Pd multilayers deposited on nanoporous TiO2 templates of different types of surface morphology. It is found that the use of templates with homogeneous and smoothed surface relief, formed on silicon wafers, ensures conservation of perpendicular anisotropy of the deposited films inherent in the continuous multilayers. Also, their magnetic hardening with doubling of the coercive field is observed. However, inhomogeneous magnetic ordering is revealed in the porous films due to the occurrence of magnetically soft regions near the pore edges and/or inside the pores. Modeling of the field dependences of magnetization and electrical resistance indicates that coherent rotation is the dominant mechanism of magnetization reversal in the porous system instead of the domain-wall motion typical of the continuous multilayers, while their magnetoresistance is determined by electron-magnon scattering, similarly to the continuous counterpart. The preservation of spin waves in the porous films indicates a high uniformity of the magnetic ordering in the fabricated porous systems due to a sufficiently regular pores array introduced into the films, despite the existence of soft-magnetic regions. The results are promising for the design and fabrication of future spintronic devices.

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish.

Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl2-exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.

Complex magnetic ordering in nanoporous [Co/Pd]5-IrMn multilayers with perpendicular magnetic anisotropy and its impact on magnetization reversal and magnetoresistance.

We have systematically investigated the magnetization reversal characteristics and magnetoresistance of continuous and nanoporous [Co/Pd]5-IrMn multilayered thin films with perpendicular magnetic anisotropy at different temperatures (4-300 K). For their nanostructuring, porosity was induced by means of deposition onto templates of anodized titania with small (∼30 nm in diameter) homogeneously distributed pores. The magnetization reversal and magnetoresistance of the porous films were found to be closely related to the splitting of the ferromagnetic material into regions with different magnetic properties, in correlation with the complex morphology of the porous system. Independent magnetization reversal is detected for these regions, and is accompanied by its strong impact on the magnetic order in the capping IrMn layer. Electron-magnon scattering is found to be a dominant mechanism of magnetoresistance, determining its almost linear field dependence in a high magnetic field and contributing to its magnetoresistance behavior, similar to magnetization reversal, in a low magnetic field. Partial rotation of IrMn magnetic moments, consistent with the magnetization reversal of the ferromagnet, is proposed as an explanation for the two-state resistance behavior observed in switching between high-resistive and low-resistive values at the magnetization reversal of the porous system studied.

Molecular Diagnosis of Drug-Resistant Tuberculosis; A Literature Review.

Drug-resistant tuberculosis is a global health problem that hinders the progress of tuberculosis eradication programs. Accurate and early detection of drug-resistant tuberculosis is essential for effective patient care, for preventing tuberculosis spread, and for limiting the development of drug-resistant strains. Culture-based drug susceptibility tests are the gold standard method for the detection of drug-resistant tuberculosis, but they are time-consuming and technically challenging, especially in low- and middle-income countries. Nowadays, different nucleic acid-based assays that detect gene mutations associated with resistance to drugs used to treat tuberculosis are available. These tests vary in type and number of targets and in sensitivity and specificity. In this review, we will describe the available molecular tests for drug-resistant tuberculosis detection and discuss their advantages and limitations.

Optimization of municipal solid waste transportation by integrating GIS analysis, equation-based, and agent-based model.

The amount of municipal solid waste (MSW) has been increasing steadily over the last decade by reason of population rising and waste generation rate. In most of the urban areas, disposal sites are usually located outside of the urban areas due to the scarcity of land. There is no fixed route map for transportation. The current waste collection and transportation are already overloaded arising from the lack of facilities and insufficient resources. In this paper, a model for optimizing municipal solid waste collection will be proposed. Firstly, the optimized plan is developed in a static context, and then it is integrated into a dynamic context using multi-agent based modelling and simulation. A case study related to Hagiang City, Vietnam, is presented to show the efficiency of the proposed model. From the optimized results, it has been found that the cost of the MSW collection is reduced by 11.3%.

Prenylated pterocarpans as bacterial neuraminidase inhibitors.

During the course of a neuraminidase inhibitor screening program on natural products, four new (6, 8, 11, and 12) and eleven known (1-5, 7, 9-10, and 13-15) pterocarpan derivatives were isolated as active principles from the EtOAc extract of the stem bark of Erythrina abyssinica. Their structures were identified by spectroscopic data analyses. All isolates exhibited significant inhibitory effects on the neuraminidases from Clostridium perfringens and Vibrio cholerae with IC(50) values ranging from 1.32 to 77.10 microM and 0.35 to 77.73 microM, respectively. The isolates (1-3, 5-8, 10, and 13-15), which possessed noncompetitive inhibition modes in kinetic studies, showed stronger activity against C. perfringens neuraminidase (IC(50) 1.32-19.82 microM) than quercetin (IC(50) 25.34 microM), which was used as the positive control. In contrast, compounds 4 and 9 behaved as competitive inhibitors and were displayed less effective (IC(50) 26.39-33.55 microM). Furthermore, calopocarpine, as a neuraminidase inhibitor, produced a decrease of V. cholerae adhesion to the host cell. Overall, these results suggest that neuraminidase inhibitors can be used in the development of new treatments to combat infectious diseases.

AMP-activated protein kinase (AMPK) activation by benzofurans and coumestans isolated from Erythrina abyssinica.

AMP-activated protein kinase (AMPK) has been proposed as a therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. The bioassay-guided fractionation of an EtOAc-soluble extract of the stem bark of Erythrina abyssinica led to the isolation of a new coumestan, erythribyssin N (1), and two new benzofurans, erythribyssin F (2) and erythribyssin H (3), along with five known compounds (4-8). When tested for their stimulatory effects on AMPK activity at a concentration of 10 muM, compounds 4 and 5 showed potent activation, while compounds 1, 2, and 7 had moderate effects. These results suggest that benzofurans and coumestans may be new lead compounds for regulating the AMPK enzyme.