Mindful attention promotes control of brain network dynamics for self-regulation and discontinues the past from the present.

Mindful attention is characterized by acknowledging the present experience as a transient mental event. Early stages of mindfulness practice may require greater neural effort for later efficiency. Early effort may self-regulate behavior and focalize the present, but this understanding lacks a computational explanation. Here we used network control theory as a model of how external control inputs-operationalizing effort-distribute changes in neural activity evoked during mindful attention across the white matter network. We hypothesized that individuals with greater network controllability, thereby efficiently distributing control inputs, effectively self-regulate behavior. We further hypothesized that brain regions that utilize greater control input exhibit shorter intrinsic timescales of neural activity. Shorter timescales characterize quickly discontinuing past processing to focalize the present. We tested these hypotheses in a randomized controlled study that primed participants to either mindfully respond or naturally react to alcohol cues during fMRI and administered text reminders and measurements of alcohol consumption during 4 wk postscan. We found that participants with greater network controllability moderated alcohol consumption. Mindful regulation of alcohol cues, compared to one's own natural reactions, reduced craving, but craving did not differ from the baseline group. Mindful regulation of alcohol cues, compared to the natural reactions of the baseline group, involved more-effortful control of neural dynamics across cognitive control and attention subnetworks. This effort persisted in the natural reactions of the mindful group compared to the baseline group. More-effortful neural states had shorter timescales than less effortful states, offering an explanation for how mindful attention promotes being present.

QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data.

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.

Edge-wise analysis reveals white matter connectivity associated with focal to bilateral tonic-clonic seizures.

OBJECTIVE: Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS. METHODS: T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices. RESULTS: Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration. SIGNIFICANCE: Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Language Recovery after Brain Injury: A Structural Network Control Theory Study.

Aphasia recovery after stroke depends on the condition of the remaining, extralesional brain network. Network control theory (NCT) provides a unique, quantitative approach to assess the interaction between brain networks. In this longitudinal, large-scale, whole-brain connectome study, we evaluated whether controllability measures of language-related regions are associated with treated aphasia recovery. Using probabilistic tractography and controlling for the effects of structural lesions, we reconstructed whole-brain diffusion tensor imaging (DTI) connectomes from 68 individuals (20 female, 48 male) with chronic poststroke aphasia who completed a three-week language therapy. Applying principles of NCT, we computed regional (1) average and (2) modal controllability, which decode the ability of a region to (1) spread control input through the brain network and (2) to facilitate brain state transitions. We tested the relationship between pretreatment controllability measures of 20 language-related left hemisphere regions and improvements in naming six months after language therapy using multiple linear regressions and a parsimonious elastic net regression model with cross-validation. Regional controllability of the inferior frontal gyrus (IFG) pars opercularis, pars orbitalis, and the anterior insula were associated with treatment outcomes independently of baseline aphasia severity, lesion volume, age, education, and network size. Modal controllability of the IFG pars opercularis was the strongest predictor of treated aphasia recovery with cross-validation and outperformed traditional graph theory, lesion load, and demographic measures. Regional NCT measures can reflect the status of the residual language network and its interaction with the remaining brain network, being able to predict language recovery after aphasia treatment.SIGNIFICANCE STATEMENT Predicting and understanding language recovery after brain injury remains a challenging, albeit a fundamental aspect of human neurology and neuroscience. In this study, we applied network control theory (NCT) to fully harness the concept of brain networks as dynamic systems and to evaluate their interaction. We studied 68 stroke survivors with aphasia who underwent imaging and longitudinal behavioral assessments coupled with language therapy. We found that the controllability of the inferior frontal regional network significantly predicted recovery in language production six months after treatment. Importantly, controllability outperformed traditional demographic, lesion, and graph-theoretical measures. Our findings shed light on the neurobiological basis of human language and can be translated into personalized rehabilitation approaches.

Altered functional brain dynamics in chromosome 22q11.2 deletion syndrome during facial affect processing.

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder associated with multiple congenital anomalies, variable medical features, and neurodevelopmental differences resulting in diverse psychiatric phenotypes, including marked deficits in facial memory and social cognition. Neuroimaging in individuals with 22q11.2DS has revealed differences relative to matched controls in BOLD fMRI activation during facial affect processing tasks. However, time-varying interactions between brain areas during facial affect processing have not yet been studied with BOLD fMRI in 22q11.2DS. We applied constrained principal component analysis to identify temporally overlapping brain activation patterns from BOLD fMRI data acquired during an emotion identification task from 58 individuals with 22q11.2DS and 58 age-, race-, and sex-matched healthy controls. Delayed frontal-motor feedback signals were diminished in individuals with 22q11.2DS, as were delayed emotional memory signals engaging amygdala, hippocampus, and entorhinal cortex. Early task-related engagement of motor and visual cortices and salience-related insular activation were relatively preserved in 22q11.2DS. Insular activation was associated with task performance within the 22q11.2DS sample. Differences in cortical surface area, but not cortical thickness, showed spatial alignment with an activation pattern associated with face processing. These findings suggest that relative to matched controls, primary visual processing and insular function are relatively intact in individuals with 22q11.22DS, while motor feedback, face processing, and emotional memory processes are more affected. Such insights may help inform potential interventional targets and enhance the specificity of neuroimaging indices of cognitive dysfunction in 22q11.2DS.

A data-driven approach for understanding the structure dependence of redox activity in humic substances.

Humic substances (HS) can facilitate electron transfer during biogeochemical processes due to their redox properties, but the structure-redox activity relationships are still difficult to describe and poorly understood. Herein, the linear (Partial Least Squares regressions; PLS) and nonlinear (artificial neural network; ANN) models were applied to monitor the structure dependence of HS redox activities in terms of electron accepting (EAC), electron donating (EDC) and overall electron transfer capacities (ETC) using its physicochemical features as input variables. The PLS model exhibited a moderate ability with R2 values of 0.60, 0.53 and 0.65 to evaluate EAC, EDC and ETC, respectively. The variable influence in the projection (VIP) scores of the PLS identified that the phenols, quinones and aromatic systems were particularly important for describing the redox activities of HS. Compared with the PLS model, the back-propagation ANN model achieved higher performance with R2 values of 0.81, 0.65 and 0.78 for monitoring the EAC, EDC and ETC, respectively. Sensitivity analysis of the ANN separately identified that the EAC highly depended on quinones, aromatics and protein-like fluorophores, while the EDC depended on phenols, aromatics and humic-like fluorophores (or stable free radicals). Additionally, carboxylic groups were the best indicator for evaluating both the EAC and EDC. Good model performances were obtained from the selected features via the PLS and sensitivity analysis, further confirming the accuracy of describing the structure-redox activity relationships with these analyses. This study provides a potential approach for identifying the structure-activity relationships of HS and an efficient machine-learning model for predicting HS redox activities.

Ceramsite made from drinking water treatment residue for water treatment: A critical review in association with typical ceramsite making.

The use of ceramsite to construct filtration systems (e.g., biofilters) is a common method for water treatment. To promote such applications, the development of low-cost, high-performance, and environmentally friendly ceramsites has received increasing attention from scientists, and a critical step in the development is the preparation of raw materials. As an inevitable and non-hazardous by-product during potable water production, drinking water treatment residue (DWTR) is typically recycled to make water treatment ceramsite to promote recycling in filtration systems. This study aims to bridge the knowledge gap regarding DWTR in making ceramsites for water treatment. The results suggest that the fabrication methods for DWTR-based ceramsite can be generally classified into sintering and non-sintering procedures. For the sintering method, owing to the heterogeneous properties (especially aluminum, iron, and calcium), DWTR has been applied as various sub-ingredients for raw materials preparations. In contrast, for the non-sintering method, DWTR is commonly applied as the main ingredient, and natural curing, physical crosslinking, and thermal treatment methods have been typically adopted to make ceramsite. However, DWTR-based ceramsites tend to have a high adsorption capability and favorable microbial effects to control different kinds of pollution (e.g., phosphorus, nitrogen, and organic matter). Future work is typically recommended to thoroughly evaluate the performance of DWTR-based ceramsite-constructed filtration systems to control water pollution concerning the making procedures, the potential to control pollution, the stability, and the safety of raw DWTR-based ceramsite, providing systematic information to design more proper planning for beneficial recycling.

Characterization of anaerobic oxidation of methane and microbial community in landfills with aeration.

Landfills are the third largest source of anthropogenic CH4 emissions. Anaerobic oxidation of methane (AOM) activity and communities of methane-oxidizing bacteria were investigated in three informal landfills in this study, namely, BJ, CH and SZ landfills, among which BJ and CH represent traditional anaerobic landfills, while the SZ landfill was subjected to aeration to accelerate waste stabilization. The AOM rates of the investigated landfilled wastes ranged from 3.66 to 23.91 nmol g-1 h-1. Among the three landfills, the AOM rate was highest in the SZ-1-Top sample, which was closest to the aeration pipe. Among the possible electron acceptors for AOM, including NO3-, NO2-, SO42- and Fe3+, the NO2--N content was the only variable that was positively correlated with the AOM rate. Compared with α-Proteobacteria methanotrophs, γ-Proteobacteria methanotrophs were more abundant in the landfilled waste, especially Methylobacter, which was detected in nearly all samples. Members of the family Methylomirabilaceae, including Candidatus Methylomirabilis, were also detected in the SZ-1 and SZ-2-Bot samples. The relative abundance of the main methanotrophs in the families Methylomonadaceae, Methylococcaceae, Rokubacteriales and Methylomirabilaceae, the genus Methylocystis and the phylum NC10 were all positive correlations with the contents of NO2--N in the landfilled waste samples. Additionally, significantly positive correlations were observed between the AOM rates and the relative abundance of the main methanotrophs except for the family Methylococcaceae. This indicated that aeration could enhance the conversion of nitrogen compounds in the landfilled waste, in which the high contents of NO2--N could stimulate the growth of methanotrophs and increase AOM rate. These findings are helpful for understanding the mechanisms of CH4 oxidation in landfills and for taking effective measures to mitigate CH4 emissions from landfills.

Ceramsite production using water treatment residue as main ingredient: The key affecting factors identification.

As an inevitable by-product of potable water production, drinking water treatment residue (DWTR) recycling to make ceramsite can provide both environmental and economic benefits in constructing filtration treatment system for water environment remediation. Given the varied properties of DWTR from different waterworks, this study aims to identify the key factors affecting ceramsite production from DWTR as main ingredient based on five different DWTR with using clay as the auxiliary material. The results showed that of sintering temperature (500-1000 °C), DWTR:clay ratio (5:5 to 9:1), sintering time (5-60 min), and granule diameter (5-15 mm), the sintering temperature was the key parameter. Increasing temperatures from 500 to 1000 °C gradually promoted DWTR sintering by enhancing Si and Al crystallization, which typically increased the formation of SiO2 and CaAl2Si2O8 crystals in ceramsite. Ceramsites made from different DWTR tended to have different properties, mainly resulting from varied contents of Si (20.2%-48.6%), K (0.0894%-2.39%), Fe (4.56%-14.3%), and loss on ignition (11.7%-39.5%). During ingredients preparation to produce up-to-standard ceramsite, supplying additional Si and diluting loss on ignition were necessary for all DWTR, while supplying K and diluting Fe may be required for specific DWTR, due to the potential varied DWTR compositions caused by different water production processes applied (e.g., type of flocculants). Further toxicity characteristic leaching procedure analysis indicated the increased leaching of Cu. However, DWTR based ceramsite was identified as non-hazardous material; even, sintering treatment reduced the leachability of Ba, Be, Cd, and Cr. DWTR based ceramsite also had relatively high specific surface area (22.1-50.5 m2/g) and could adsorb Cd, Cu, and Pb from solution. Overall, based on appropriate management, DWTR can be recycled as the main ingredient in the production of ceramsite for water environment remediation.

Characterizing the hyper- and hypometabolism in temporal lobe epilepsy using multivariate machine learning.

Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy, presenting both structural and metabolic abnormalities in the ipsilateral mesial temporal lobe. While it has been demonstrated that the metabolic abnormalities in MTLE actually extend beyond the epileptogenic zone, how such multidimensional information is associated with the diagnosis of MTLE remains to be tested. Here, we explore the whole-brain metabolic patterns in 23 patients with MTLE and 24 healthy controls using [18 F]fluorodeoxyglucose PET imaging. Based on a multivariate machine learning approach, we demonstrate that the brain metabolic patterns can discriminate patients with MTLE from controls with a superior accuracy (>95%). Importantly, voxels showing the most extreme contributing weights to the classification (i.e., the most important regional predictors) distribute across both hemispheres, involving both ipsilateral negative weights over the anterior part of lateral and medial temporal lobe, posterior insula, and lateral orbital frontal gyrus, and contralateral positive weights over the anterior frontal lobe, temporal lobe, and lingual gyrus. Through region-of-interest analyses, we verify that in patients with MTLE, the negatively weighted regions are hypometabolic, and the positively weighted regions are hypermetabolic, compared to controls. Interestingly, despite that both hypo- and hypermetabolism have mutually contributed to our model, they may reflect different pathological and/or compensative responses. For instance, patients with earlier age at epilepsy onset present greater hypometabolism in the ipsilateral inferior temporal gyrus, while we find no evidence of such association with hypermetabolism. In summary, quantitative models utilizing multidimensional brain metabolic information may provide additional assistance to presurgical workups in TLE.

Comparison of Detection Methods of Microplastics in Landfill Mineralized Refuse and Selection of Degradation Degree Indexes.

A landfill is an important sink of plastic waste and potential sources of microplastics (MPs) when mineralized refuse is reused. However, limitations are still present in quantifying MPs in mineralized refuse and assessing their degradation degree. In this study, laser direct infrared spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify MPs of mineralized refuse from a landfill. Although 25-113 items/g MPs were detected in particles subjected to flotation, 37.9-674 µg/g polyethylene terephthalate (PET) and 0.0716-1.01 µg/g polycarbonate (PC) were detected in the residual solids by LC-MS/MS, indicating a great amount of plastic polymers still presented in the residue. This suggests that the commonly used flotation-counting method will lead to significant underestimation of MP pollution in mineralized refuse, which might be due to the aging and aggregation process caused by the long-term landfill process. The ratio of "bisphenol A/PC" and "plasticizer/MPs" was found to be positively correlated and negatively correlated with the landfill age, respectively. Therefore, in addition to the spectral index such as the carbonyl index, new indexes based on the concentrations of polymers, free monomers, and plasticizers were proposed to characterize the degradation degree of MPs in a landfill.

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

Dissolved Silicate Enhances the Oxidation of Chlorophenols by Permanganate: Important Role of Silicate-Stabilized MnO2 Colloids.

Dissolved silicate is an important background constituent of natural waters, but there is little clarity regarding the effect of silicate on the oxidizing capability of permanganate (Mn(VII)) and on its efficiency for remediation applications. In the present study, we found that dissolved silicate, metasilicate or disilicate (DS), could significantly promote the oxidation of 2,4-dichlorophenol (2,4-DCP) by Mn(VII), and the extent of the promoting effect was even more evident than that of pyrophosphate (PP). The experiments showed that, unlike PP, DS was not capable of coordinating with Mn(III) ions, and the promoting effect of DS was not due to the oxidizing capability of complexed Mn(III). Instead, DS ions, as a weak base, could combine with the hydroxyl groups of MnO2 via hydrogen bonding to limit the growth of colloidal MnO2 particles. The DS-stabilized colloidal MnO2 particles, with hydrodynamic diameters less than 100 nm, could act as catalysts to enhance the oxidation of 2,4-DCP by Mn(VII). The best promoting effect of DS on the performance of Mn(VII) oxidant was achieved at the initial solution pH of 7, and the coexisting bicarbonate ions further improved the oxidation of 2,4-DCP in the Mn(VII)/DS system. Sand column experiments showed that the combined use of Mn(VII) and DS additive could mitigate the problem of permeability reduction of sand associated with the retention of MnO2 particles. This study not only deepens our understanding on the role of dissolved silicate in a Mn(VII) oxidation process but also provides an effective and green method to enhance the oxidizing capacity of Mn(VII)-based treatment systems.

Diminished B-Cell Response After Repeat Influenza Vaccination.

Annual vaccination with influenza vaccines is recommended for protection against influenza in the United States. Past clinical studies and meta-analysis, however, have reported conflicting results on the benefits of annual vaccination. B-cell responses elicited following repeat influenza vaccinations over multiple seasons have not been examined in detail. We analyzed the B-cell and antibody (Ab) responses in volunteers vaccinated yearly, from 2010 or 2011 through 2014, with seasonal trivalent inactivated influenza vaccines. Statistical analyses were designed to help correct for possible bias due to reduced sample size in the later years of the study. We show that, after the second annual vaccination, the frequency of vaccine-specific plasmablasts and the binding reactivity of plasmablast-derived polyclonal Abs are reduced and do not increase in subsequent years. Similar trends are observed with the serum hemagglutination inhibition Ab response after each annual vaccination, as well as the binding reactivity of plasmablast-derived polyclonal Abs to the hemagglutinin of influenza A virus vaccine components, even with changes in the seasonal vaccine components during the study. Our findings indicate a diminished B-cell response to annual vaccination with seasonal trivalent influenza vaccine. These results emphasize the need for developing improved strategies to enhance the immunogenicity and efficacy of annual influenza vaccination.

Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an abnormal accumulation of amyloid-ß (Aß) plaques, neuroinflammation, and impaired neurogenesis. Urolithin A (UA), a gut-microbial metabolite of ellagic acid, has been reported to exert anti-inflammatory effects in the brain. However, it is unknown whether UA exerts its properties of anti-inflammation and neuronal protection in the APPswe/PS1ΔE9 (APP/PS1) mouse model of AD. METHODS: Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia, Aß deposition, and neurogenesis. The expression of inflammatory mediators were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The modulating effects of UA on cell signaling pathways were assayed by Western blotting. RESULTS: We demonstrated that UA ameliorated cognitive impairment, prevented neuronal apoptosis, and enhanced neurogenesis in APP/PS1 mice. Furthermore, UA attenuated Aß deposition and peri-plaque microgliosis and astrocytosis in the cortex and hippocampus. We also found that UA affected critical cell signaling pathways, specifically by enhancing cerebral AMPK activation, decreasing the activation of P65NF-κB and P38MAPK, and suppressing Bace1 and APP degradation. CONCLUSIONS: Our results indicated that UA imparted cognitive protection by protecting neurons from death and triggering neurogenesis via anti-inflammatory signaling in APP/PS1 mice, suggesting that UA might be a promising therapeutic drug to treat AD.

JAK2/STAT3 signaling mediates IL-6-inhibited neurogenesis of neural stem cells through DNA demethylation/methylation.

Neuroinflammation, considered as a pathological hallmark of Alzheimer's disease (AD), has been demonstrated to affect hippocampal neurogenesis and cognitive function. Interleukin-6 (IL-6) is a proinflammatory cytokine known to modulate neurogenesis. However, the mechanisms are still largely unknown. Here, we reported that IL-6 suppressed neurogenesis via a JAK2/STAT3 signaling in neural stem cells (NSCs). Importantly, we found that NeuroD1 (Neurogenic differentiation 1) gene expression, which drives NSCs neurodifferentiation, was regulated by TET3 and DNMT1 in a JAK2/STAT3-dependent manner. We further found that JAK2/STAT3 inhibition enhanced demethylation of NeuroD1 regulatory elements in IL-6-treated cells, which is related to the significant upregulation of TET3 expression as well as the decreased expression of DNMT1. Furthermore, Inhibiting JAK2/STAT3 significantly rescued the memory deficits and hippocampal neurogenesis dysfunction in APP/PS1 mice. Our data suggest that JAK2/STAT3 signaling plays a vital role in suppressing neurogenesis of NSCs exposed to IL-6 at the epigenetic level, by regulating DNA methylation/demethylation.

Disrupted dynamic network reconfiguration of the language system in temporal lobe epilepsy.

Temporal lobe epilepsy tends to reshape the language system causing maladaptive reorganization that can be characterized by task-based functional MRI, and eventually can contribute to surgical decision making processes. However, the dynamic interacting nature of the brain as a complex system is often neglected, with many studies treating the language system as a static monolithic structure. Here, we demonstrate that as a specialized and integrated system, the language network is inherently dynamic, characterized by rich patterns of regional interactions, whose transient dynamics are disrupted in patients with temporal lobe epilepsy. Specifically, we applied tools from dynamic network neuroscience to functional MRI data collected from 50 temporal lobe epilepsy patients and 30 matched healthy controls during performance of a verbal fluency task, as well as during rest. By assigning 16 language-related regions into four subsystems (i.e. bilateral frontal and temporal), we observed regional specialization in both the probability of transient interactions and the frequency of such changes, in both healthy controls and patients during task performance but not rest. Furthermore, we found that both left and right temporal lobe epilepsy patients displayed reduced interactions within the left frontal 'core' subsystem compared to the healthy controls, while left temporal lobe epilepsy patients were unique in showing enhanced interactions between the left frontal 'core' and the right temporal subsystems. Also, both patient groups displayed reduced flexibility in the transient interactions of the left temporal and right frontal subsystems, which formed the 'periphery' of the language network. Importantly, such group differences were again evident only during task condition. Lastly, through random forest regression, we showed that dynamic reconfiguration of the language system tracks individual differences in verbal fluency with superior prediction accuracy compared to traditional activation-based static measures. Our results suggest dynamic network measures may be an effective biomarker for detecting the language dysfunction associated with neurological diseases such as temporal lobe epilepsy, specifying both the type of neuronal communications that are missing in these patients and those that are potentially added but maladaptive. Further advancements along these lines, transforming how we characterize and map language networks in the brain, have a high probability of altering clinical decision making in neurosurgical centres.10.1093/brain/awy042_video1awy042media15754656112001.

The impacts of metal ions on phytotoxicity mediate by microbial community during municipal solid waste composting.

Metal ions (MIs) are the main sources of phytotoxicity of compost product, which can be absorbed by plants, thereby reducing the germination rate. The aim of this study was to analyze the interactional mechanism among MIs, microbial community, the structure of water soluble organic matter and phytotoxicity during composting. The results indicated that phytotoxicity was positively correlated with MIs (II) (As, Cd, Hg, Cr, Fe, Mn and Pb), and negatively correlated with MIs (I) (Mg, Zn, Ni and Cu). Furthermore, SO42-, organic matter (OM), pH and four bacterial species significantly influenced the association of MIs to phytotoxicity. Additionally, molecular weight, protein-like substance and oxygen-containing functional groups relating to MIs (II) were significantly influenced by the nine bacterial species. Based on the response of physicochemical parameters on these key bacterial species, three possible mutual mechanisms were proposed using the structural equation model. Accordingly, a regulating method was proposed to reduce the phytotoxicity during composting.

Spatial distribution of organochlorine and organophosphorus pesticides in soil-groundwater systems and their associated risks in the middle reaches of the Yangtze River Basin.

Soil and groundwater samples were collected from paddy fields in the middle reaches of the Yangtze River Basin to study the occurrence and the risks associated with organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in soil and groundwater. Results showed that OCPs and OPPs were widely distributed throughout the study area. The levels of OCPs and OPPs in the soil were much lower than those specified by soil quality standards. However, the levels of four OCPs (heptachlors, aldrin, dieldrin, and γ-hexachlorocyclohexane) in groundwater were higher than those permitted by drinking water standards. The health risk assessment method suggested by the US Environment Protection Agency was used to evaluate the regional risks from selected pesticides. Results showed that there were low health risks from OCPs and OPPs in soil at the regional scale, but high risks from heptachlor, aldrin, and endrin in groundwater, suggesting an urgent need for groundwater protection. There are widespread concerns on dichlorodiphenyltrichloroethane and hexachlorocyclohexane, but little focus on other pesticides in China. However, our results suggest that the presence of, and risks from, other pesticides in groundwater should be a focus from the region aspect.