Multilevel Screening Strategy to Identify the Hydrophobic Organic Components of Ambient PM2.5 Associated with Hepatocellular Steatosis.

Hepatic steatosis is the first step in a series of events that drives hepatic disease and has been considerably associated with exposure to fine particulate matter (PM2.5). Although the chemical constituents of particles matter in the negative health effects, the specific components of PM2.5 that trigger hepatic steatosis remain unclear. New strategies prioritizing the identification of the key components with the highest potential to cause adverse effects among the numerous components of PM2.5 are needed. Herein, we established a high-resolution mass spectrometry (MS) data set comprising the hydrophobic organic components corresponding to 67 PM2.5 samples in total from Taiyuan and Guangzhou, two representative cities in North and South China, respectively. The lipid accumulation bioeffect profiles of the above samples were also obtained. Considerable hepatocyte lipid accumulation was observed in most PM2.5 extracts. Subsequently, 40 of 695 components were initially screened through machine learning-assisted data filtering based on an integrated bioassay with MS data. Next, nine compounds were further selected as candidates contributing to hepatocellular steatosis based on absorption, distribution, metabolism, and excretion evaluation and molecular dockingin silico. Finally, seven components were confirmed in vitro. This study provided a multilevel screening strategy for key active components in PM2.5 and provided insight into the hydrophobic PM2.5 components that induce hepatocellular steatosis.

Establishment of a prognostic model toward lung squamous cell carcinoma based on m7G-related genes in the cancer genome atlas.

Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (m7G) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, expression of m7G-related genes in LUSC and their association with prognosis remain unclear. In the present study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent nontumor lung tissue reports). The genes included six upregulated genes (KLK7, LCE3E, AREG, KLK6, ZBED2, and MAPK4) and three downregulated genes (ADH1C, NTS, and ERLIN2). Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine m7G-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways including antigen processing and presentation, adherent plaques, extracellular matrix receptor interactions, drug metabolism of cytochrome P-450, and metabolism of cytochrome P-450 to xenobiotics; the functions of these genes are likely accomplished in part by m6A modifications. The effect of m7G-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis.NEW & NOTEWORTHY Based on the differential expression of 7-methylguanosine (m7G) modification-associated genes between normal and lung squamous cell carcinoma (LUSC) tissues, and considering the performance of our m7G-related gene risk profiles as independent risk factors in predicting overall survival, we conclude that m7G modification is closely linked to the development of LUSC. In addition, this study offers a new genetic marker for predicting the prognosis of patients with LUSC and presents a crucial theoretical foundation for future investigations on the relationship between m7G modification-related genes, immunity, and drug sensitivity in LUSC.

Estrogen deficiency impedes fracture healing despite eliminating the excessive absorption of the posterior callus in a semi-fixed distal tibial fracture mouse model.

BACKGROUND: Treatment of distal tibial fractures is a challenge due to their specific anatomical location. However, there is no appropriate mouse model to simulate a clinical distal tibial fracture for basic research. The aim of this investigation was to evaluate the feasibility of simulating a clinical fracture of the distal tibia of mice and to investigate the effect of ovariectomy (OVX)-induced osteoporosis on fracture healing in this model. METHODS: Sixty female 8-week-old C57BL/6 mice were randomly divided into two groups, either sham or OVX. A semi-fixation distal tibia fracture was established in the right tibia after 8 weeks of OVX. The right tibias were collected at 7, 14, 21, and 28 days post fracture. RESULTS: In the semi-fixation distal tibia fracture model, the posterior callus in the sham group showed excessive bone resorption and lower bone mass phenotype compared with the anterior site; a similar trend was not found in the OVX group. At 28 days post fracture, the posterior callus was more mineralized than the anterior callus in the OVX group. Although the fracture healing of the sham group showed a special phenotype in this mode, the progress and quality of fracture healing were still better than those of the OVX group. CONCLUSION: A semi-fixed distal tibial closed fracture mouse model was successfully established. In this model, excess bone resorption of the posterior callus impaired normal fracture healing, but not in OVX-induced osteoporotic bone. Although the stress shielding effect was not observed in the OVX group, impaired bone healing caused by OVX was still present. Our results suggest that this fracture model may have potential for studies on distal tibial fractures and stress shielding.

Protection of melatonin against acidosis-induced neuronal injuries.

Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome-related signals, imbalanced oxidative stress/anti-oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10-4  mol/L) was used to pre-treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis-induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase-3ß and nuclear factor-κB signals, ER stress and Golgi stress, and the abnormal autophagy-lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis-induced injuries.

Oxidative injury induced by cadmium sulfide nanoparticles in A549 cells and rat lungs.

BACKGROUND: Rod-shaped cadmium sulfide nanoparticles (CdS NPs) are becoming increasingly important in many industrial fields, but their potential hazards remain unknown. OBJECTIVES: This study aimed to explore the patterns and mechanisms of lung injury induced by CdS NPs. METHODS: A549 cells and rats were exposed to two types of CdS NPs with a same diameter of 20-30 nm but different lengths, CdS1 (80-100 nm) and CdS2 (110-130 nm). The using doses were included 10 µg/ml and 20 µg/ml two types of CdS NPs for cellular experiments and five times dose of 20 mg/kg body weight for rats' exposure. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and trypan blue staining were used to detect the A549 cell mortality percentage. The levels of reactive oxygen species (ROS) were determined in A549 cell. The vigor of superoxide dismutase (SOD) and the contents of catalase (CAT) and malondialdehyde (MDA) were detected both in A549 cells and in rats' serum and lung tissues. The cellular morphological changes were observed under transmission electron microscopy (TEM) and the pathological changes were observed in rats' lung tissue. RESULTS: CdS NPs significantly increased A549 cell mortality percentage. The CdS NPs also increased the levels of ROS and MDA content, whereas they decreased SOD and CAT activities. In parallel, similar changes of the contents of MDA, SOD and CAT were also observed in the sera and lung tissues of CdS NP-treated rats. The cellular TEM detection revealed that two types of CdS nanorods appeared as orderly arranged rounded fat droplets separately and leading to nucleus condensation (CdS1). These cellular and rats' tissues changes in the group treated with CdS1 were more significant than the CdS2 groups. Furthermore, CdS NPs induced many pathological changes, including emphysematous changes in rat lung tissue. Especially visible lung consolidation can be observed in the CdS1 group. CONCLUSIONS: CdS NPs induce oxidative injury in the respiratory system, and their toxic effects may be related to grain length.

[Effects of nano-lead exposure on learning and memory as well as iron homeostasis in brain of offspring rats].

OBJECTIVE: To investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42). METHODS: Twenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay. RESULTS: After nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05). ONCLUSION: n Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

[Study of quercetin on pulmonary fibrosis by silica particles].

OBJECTIVE: To observe the intervention effect of quercetin to silica dust cause pulmonary fibrosis. METHODS: Forty-eight healthy male adult SPF SD rats were selected and they were randomly divided into six groups (control group, 7 d,14 d,21 d and 28d dust group, preventive group). Rats in the control group were administrated 1 ml saline via trachea injection. Rats in dust group and preventive group were give silica solution for 1ml at dose of 50 mg/ml, and the prevention group with quercetin of 50 mg/kg every day lavage treatment intervention. In building on days 7,14,21,28 later, the lung tissue were removaled to HE staining for determining the degree of alveolitis and pulmonary fibrosis. The content of hydroxyproline (HYP) and the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) were detected by using the kits. RESULTS: Alveolar septal edema, inflammatory cell infiltration and fibrosis were not found in control group. In the preventive group, lots of inflammatory cells infiltration were observed on days 7. Inflammatory cells were reduced, the number of the fibroblasts and matrix in alveolar septum were obviously increased, and alveolar structure was damaged on day 14. Pulmonary fibrosis was increased, severe fibrosis was found on day 28. Silicon dust after infected lung tissue expression of HYP content increased, the activity of CAT and GSH-Px decrease gradually. After joining quercetin the expression of HYP content gradually reduce, CAT and GSH-Px activity increased, the difference was statistically significant (P<0.05). CONCLUSION: Quercetin of silica dust caused by pulmonary fibrosis have certain prevention.

[Regulation of ursolic acid on TNF-alpha and collagen in silicotic rats].

OBJECTIVE: To explore the regulation of ursolic acid on the expressions of TNF-alpha and collagen on Silicotic Rats. METHODS: Seventy-five Wistar rats (class SPF) were divided into there groups according to the randomized block design, namely, control, model, ursolic acid groups with twenty-five rats in each group. SiO2 powders (250 mg/kg) were douched in the trachea of rat to make the silicotic model in model and ursolic acid groups. Ursolic acid (40 mg/kg) was injected into stomach cavity in ursolic acid group from the second day of SiO2, while the rats in control group were given sodium chloride in the same condition for 28 consecutive days. All rats were put to death on the 7th,14th and 28th day. TNF-alpha contents in serum were detected by ELISA. Total collagen contents in lung tissue were determined by hydroxyproline kits. Collagen I and III in lung tissue were investigated by western blot technique. RESULTS: After four weeks of intervention, the contents of TNF-alpha in serum of the model group had rised, showing statistically significant difference in each time compared to those of the control group (P < 0.05). Ursolic acid had depressant effect on the contents of TNF-alpha (P < 0.05). Compared with control group, the content of total collagen was significantly improved in model group (P < 0.05). However, ursolic acid depressed the expression of total collagen protein compared to those of the model group (P < 0.05). The expression levels of collagen I and III in ursolic acid and model groups were similar with the total collagen. CONCLUSIONS: Ursolic acid could decrease the expressions of TNF-alpha and collagen in the process of silicosis fibrosis.

Ferroelectric modulation of CuCo2O4 nanorods for controllable alkaline water electrolysis.

As a technology for emerging environmental applications, water electrolysis is a significant approach for producing clean hydrogen energy. In this work, we used an efficacious piezoelectric method to significantly improve the catalytic water splitting activity without affecting the morphology as well as the components by altering the bulk charge separation state inside the material. The obtained CuCo2O4 nanorods were treated under a corona polarization apparatus, which significantly enhanced ferroelectricity relative to that before the polarization increasing the physical charge separation and piezoelectric potential energy, enhancing the green hydrogen production. The polarized CuCo2O4 nanorods exhibit excellent water electrolysis performance under alkaline conditions, with hydrogen evolution overpotential of 78.7 mV and oxygen evolution overpotential of 299 mV at 10 mA cm-2, which is much better than that of unpolarized CuCo2O4 nanorods. Moreover, the Tafel slopes of polarized CuCo2O4 nanorods are 86.9 mV dec-1 in the HER process and 73.1 mV dec-1 in the OER process, which are much lower than commercial catalysts of Pt/C (88.0 mV dec-1 for HER) or RuO2 (78.5 mV dec-1 for OER), proving faster kinetic on polarized CuCo2O4 nanorods due to their higher electroconductibility and intrinsic activity. In particular, polarized CuCo2O4 nanorods are identified as promising catalysts for water electrolysis with robust stability, offering outstanding catalytic performance and excellent energy efficiency.

[Disorder of copper homeostasis induced by lead exposure among mice and intervention effect of quercetin].

OBJECTIVE: To investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin. METHODS: Twenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus. RESULTS: The Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced. CONCLUSION: Lead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.

Local Causal Discovery in Multiple Manipulated Datasets.

We consider the problem of distinguishing direct causes from direct effects of a target variable of interest from multiple manipulated datasets with unknown manipulated variables and nonidentical data distributions. Recent studies have shown that datasets attained from manipulated experiments (i.e., manipulated data) contain richer causal information than observational data for causal structure learning. Thus, in this article, we propose a new algorithm, which makes full use of the interventional properties of a causal model to discover the direct causes and direct effects of a target variable from multiple datasets with different manipulations. It is more suited to real-world cases and is also a challenge to be addressed in this article. First, we apply the backward framework to learn parents and children (PC) of a given target from multiple manipulated datasets. Second, we orient some edges connected to the target in advance through the assumption that the target variable is not manipulated and then orient the remaining undirected edges by finding invariant V-structures from multiple datasets. Third, we analyze the correctness of the proposed algorithm. To the best of our knowledge, the proposed algorithm is the first that can identify the local causal structure of a given target from multiple manipulated datasets with unknown manipulated variables. Experimental results on standard Bayesian networks validate the effectiveness of our algorithm.

Evaluating Classification Model Against Bayes Error Rate.

For a classification task, we usually select an appropriate classifier via model selection. How to evaluate whether the chosen classifier is optimal? One can answer this question via Bayes error rate (BER). Unfortunately, estimating BER is a fundamental conundrum. Most existing BER estimators focus on giving the upper and lower bounds of the BER. However, evaluating whether the selected classifier is optimal based on these bounds is hard. In this article, we aim to learn the exact BER instead of bounds on BER. The core of our method is to transform the BER calculation problem into a noise recognition problem. Specifically, we define a type of noise called Bayes noise and prove that the proportion of Bayes noisy samples in a data set is statistically consistent with the BER of the data set. To recognize the Bayes noisy samples, we present a method consisting of two parts: selecting reliable samples based on percolation theory and then employing a label propagation algorithm to recognize the Bayes noisy samples based on the selected reliable samples. The superiority of the proposed method compared to the existing BER estimators is verified on extensive synthetic, benchmark, and image data sets.

The fabrication and evaluation of silver nanoparticle-based keratin scaffolds.

The biotoxicity caused by focus releasing of Ag, which associated with the Ag loading mode, is a problematic issue that need to be solved for practical utilization of the keratin based wound dressing. In this study, keratin/AgNPs blend scaffolds (Ker/Ag) and keratin scaffolds with AgNPs attached on the scaffold's wall surface (Ag@Ker) were prepared. Structure and physical properties of the scaffolds were tested and investigated. In comparison to the Ag@Ker scaffolds, the Ker/Ag scaffolds with uniform dispersion of AgNPs have larger tensile strength and slower degradation rate. Both kind of scaffolds present excellent antibacterial property with 10 µg mL-1 AgNPs addition, while the Ker/Ag displayed a linear Ag releasing ratio in the first 5-7 days, which is beneficial for obtaining a continuous antibacterial property and avoiding the biotoxicity caused by focus release of Ag. Correspondingly, cytotoxicity assay further reveals that the continuously slow release of Ag of the Ker/Ag scaffolds accelerated the proliferation of cell. Infectious animal models and histological studies showed that the Ker/Ag scaffolds can effectively inhibit the inflammatory response and accelerate epithelialization. Thus, it can be concluded that the Ker/Ag scaffolds with uniform dispersion of AgNPs are more attractive as wound repair materials.

Upregulation of astrocytes protein phosphatase-2A stimulates astrocytes migration via inhibiting p38 MAPK in tg2576 mice.

One of the earliest neuropathological changes in Alzheimer disease (AD) is the accumulation of astrocytes at sites of ß-amyloid (Aß) deposits, but the cause of this cellular response is unclear. As the activity of protein phosphatase 2A (PP2A) is significantly decreased in the AD brains, we studied the role of PP2A in astrocytes migration. We observed unexpectedly that PP2A activity associated with glial fibrillary acidic protein, an astrocyte marker, was significantly upregulated in tg2576 mice, demonstrated by an increased enzyme activity, a decreased demethylation at leucine-309 (DM-PP2Ac), and a decreased phosphorylation at tyrosine-307 of PP2A (pY307-PP2Ac). Further studies by using in vitro wound-healing model and transwell assay demonstrated that upregulation of PP2A pharmacologically and genetically could stimulate astrocytes migration. Activation of PP2A promotes actin organization and inhibits p38 mitogen-activated protein kinases (p38 MAPK), while simultaneous activation of p38 MAPK partially abolishes the PP2A-induced astrocytes migration. Our data suggest that activation of astrocytes PP2A in tg2567 mice may stimulate the migration of astrocytes to the amyloid plaques by p38 MAPK inhibition, implying that PP2A deficits observed in AD may cause Aß accumulation via hindering the astrocytes migration.

Causal Feature Selection With Dual Correction.

Causal feature selection methods aim to identify a Markov boundary (MB) of a class variable, and almost all the existing causal feature selection algorithms use conditional independence (CI) tests to learn the MB. However, in real-world applications, due to data issues (e.g., noisy or small samples), CI tests can be unreliable; thus, causal feature selection algorithms relying on CI tests encounter two types of errors: false positives (i.e., selecting false MB features) and false negatives (i.e., discarding true MB features). Existing algorithms only tackle either false positives or false negatives, and they cannot deal with both types of errors at the same time, leading to unsatisfactory results. To address this issue, we propose a dual-correction-strategy-based MB learning (DCMB) algorithm to correct the two types of errors simultaneously. Specifically, DCMB selectively removes false positives from the MB features currently selected, while selectively retrieving false negatives from the features currently discarded. To automatically determine the optimal number of selected features for the selective removal and retrieval in the dual correction strategy, we design the simulated-annealing-based DCMB (SA-DCMB) algorithm. Using benchmark Bayesian network (BN) datasets, the experimental results demonstrate that DCMB achieves substantial improvements on the MB learning accuracy compared with the existing MB learning methods. Empirical studies in real-world datasets validate the effectiveness of SA-DCMB for classification against state-of-the-art causal and traditional feature selection algorithms.

Dual-Representation-Based Autoencoder for Domain Adaptation.

Domain adaptation aims to facilitate the learning task in an unlabeled target domain by leveraging the auxiliary knowledge in a well-labeled source domain from a different distribution. Almost existing autoencoder-based domain adaptation approaches focus on learning domain-invariant representations to reduce the distribution discrepancy between source and target domains. However, there is still a weakness existing in these approaches: the class-discriminative information of the two domains may be damaged while aligning the distributions of the source and target domains, which makes the samples with different classes close to each other, leading to performance degradation. To tackle this issue, we propose a novel dual-representation autoencoder (DRAE) to learn dual-domain-invariant representations for domain adaptation. Specifically, DRAE consists of three learning phases. First, DRAE learns global representations of all source and target data to maximize the interclass distance in each domain and minimize the marginal distribution and conditional distribution of both domains simultaneously. Second, DRAE extracts local representations of instances sharing the same label in both domains to maintain class-discriminative information in each class. Finally, DRAE constructs dual representations by aligning the global and local representations with different weights. Using three text and two image datasets and 12 state-of-the-art domain adaptation methods, the extensive experiments have demonstrated the effectiveness of DRAE.

Brain copper clearance by the blood-cerebrospinal fluid-barrier: Effects of lead exposure.

Lead (Pb) is a heavy metal commonly found in the environment and is known to have neurotoxic, hematological, and other toxic effects. It has been reported that Pb exposure can disturb metal regulation in the blood-cerebrospinal fluid-barrier (BCB). Copper (Cu) plays a key role in maintaining normal brain function and can accumulate in the brain after Pb exposure. However, the mechanism by which Pb affects Cu levels in the brain is still unknown. This study investigated Cu clearance by the BCB in the central nervous system (CNS) of Sprague-Dawley rats after Pb exposure by focusing on the Cu transporter protein CTR1/ATP7A. Inductively coupled plasma mass spectrometry (ICP-MS) was used to examine how heavy metal levels change in the hippocampus, cortex, and cerebrospinal fluid (CSF) after Pb exposure. Ventriculo-cisternal perfusion measurements suggested that the ability of the BCB to deliver Cu from the CSF to the blood decreased after Pb exposure. The presence of excess Cu in the choroid plexus led to CTR1/ATP7A shifting toward the apical microvilli facing the CSF after Pb exposure. We further evaluated microstructure of the choroid plexus by transmission electron microscopy, revealing altered mitochondrial morphology with decreased microvilli after Pb exposure. Conclusively, exposure to Pb alters the cellular structure of the BCB and its Cu clearance function, which can cause further brain damage.

Relationship of adult neurogenesis with tau phosphorylation and GSK-3ß activity in subventricular zone.

Altered neurogenesis has been reported in Alzheimer disease (AD), the most common neurodegenerative disorder characterized with hyperphosphorylated tau and accumulation of ß-amyloid (Aß). Recent studies suggest that tau phosphorylation is essential for hippocampal neurogenesis, however, it is not known whether tau phosphorylation also play a role in neurogenesis of subventricular zone (SVZ), another main progenitor niche in the brain. Here, we examined the expression of phosphorylated tau (p-tau) in SVZ and analyzed the role of p-tau in adult SVZ neurogenesis. We found that the expression of p-tau increased during postnatal development and remains at a high level until adulthood, and the p-tau was colocalized with some SVZ neural precursors. However, up-regulating glycogen synthase kinase-3 (GSK-3), a crucial tau kinase, had no effect on SVZ neurogenesis in adult rat brain. The SVZ neurogenesis was also unaffected in tau knockout and human tau transgenic mice. These results suggest that tau phosphorylation and GSK-3 activation may not be essential for adult SVZ neurogenesis.

Semi-Supervised Clustering With Constraints of Different Types From Multiple Information Sources.

Semi-supervised clustering is one of important research topics in cluster analysis, which uses pre-given knowledge as constraints to improve the clustering performance. While clustering a data set, people often get prior constraints from different information sources, which may have different representations and contents, to guide clustering process. However, most of existing semi-supervised clustering algorithms are based on single-source constraints and rarely consider to integrate multi-source constraints to enhance the clustering quality. To solve the problem, we analyze the relations among different types of constraints and propose an uniform representation for them. Based it, we propose a new semi-supervised clustering algorithm to find out a clustering that has good cluster structure and high consensus of all the sources of constraints. In the algorithm, we construct an optimization objective model and its solution method to achieve the aim. This algorithm can integrate multi-source constraints well to reduce the effect of incorrect constraints from single sources and find out a high-quality clustering. By the experimental studies on several benchmark data sets, we illustrate the effectiveness of the proposed algorithm, compared to other semi-supervised clustering algorithms.

Essential role of tau phosphorylation in adult hippocampal neurogenesis.

An increased hippocampal neurogenesis has been observed in Alzheimer disease (AD), the most common neurodegenerative disorder characterized with accumulation of ß-amyloid (Aß) and hyperphosphorylated tau (p-tau). Studies in transgenic mouse models suggest that the amyloidosis suppresses adult neurogenesis. Although emerging evidence links tau to neurodevelopment, the direct data regarding tau phosphorylation in adult neurogenesis is missing. Here, we found that the immature neurons, identified by doublecortin (DCX) and neurogenic differentiation factor (neuroD), were only immunoreactive to p-tau but not to the non-p-tau in adult rat brain and human patients with AD, and the p-tau was coexpressed temporally and spatially with DCX and neuroD in the hippocampal dentate gyrus (DG) of the rat brains during postnatal development. A correlative increase of immature neuron markers and tau phosphorylation was induced in rat hippocampal DG by upregulating glycogen synthase kinase-3 (GSK-3), a crucial tau kinase, and the increased neurogenesis was due to an enhanced proliferation but not survival or differentiation of the newborn neurons. The hippocampal neurogenesis was severely impaired in tau knockout mice and activation of GSK-3 in these mice did not rescue the deficits. These results reveal an essential role of tau phosphorylation in adult hippocampal neurogenesis. It suggests that spatial/temporal manipulation of tau phosphorylation may be compensatory for the neuron loss in neurological disorders, including AD.