Relationship Between Reactive Astrocytes, by [18F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer's Disease.

Reactive astrocytes play an important role in the development of Alzheimer's disease (AD). Here, we aimed to investigate the temporospatial relationships among monoamine oxidase-B, tau and amyloid-ß (Aß), translocator protein, and glucose metabolism by using multitracer imaging in AD transgenic mouse models. Positron emission tomography (PET) imaging with [18F]SMBT-1 (monoamine oxidase-B), [18F]florbetapir (Aß), [18F]PM-PBB3 (tau), [18F]fluorodeoxyglucose (FDG), and [18F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3×Tg mice, and aged-matched wild-type mice. The brain regional referenced standard uptake value (SUVR) was computed with the cerebellum as the reference region. Immunofluorescence staining was performed on mouse brain tissue slices. [18F]SMBT-1 and [18F]florbetapir SUVRs were greater in the cortex and hippocampus of 10-month-old APP/PS1 mice than in those of 5-month-old APP/PS1 mice and wild-type mice. No significant difference in the regional [18F]FDG or [18F]DPA-714 SUVRs was observed in the brains of 5- or 10-month-old APP/PS1 mice or wild-type mice. No significant difference in the SUVRs of any tracer was observed between 11-month-old 3×Tg mice and age-matched wild-type mice. A positive correlation between the SUVRs of [18F]florbetapir and [18F]DPA-714 in the cortex and hippocampus was observed among the transgenic mice. Immunostaining validated the distribution of MAO-B and limited Aß and tau pathology in 11-month-old 3×Tg mice; and Aß deposits in brain tissue from 10-month-old APP/PS1 mice. In summary, these findings provide in vivo evidence that an increase in astrocyte [18F]SMBT-1 accompanies Aß accumulation in APP/PS1 models of AD amyloidosis.

Reduced SV2A and GABAA receptor levels in the brains of type 2 diabetic rats revealed by [18F]SDM-8 and [18F]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 (GABAA) receptor, amyloid-ß, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats. METHODS: Positron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAA receptor), [18F]florbetapir (amyloid-ß), [18F]PM-PBB3 (tau), and [18F]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 [18F]SDM-8 uptake and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. The regional uptake of [18F]florbetapir and [18F]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 GABAA 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 GABAA receptor levels in the brains of aged T2DM ZDF rats.

Brain glucose metabolism and dopamine transporter changes in rats with morphine-induced conditioned place preference.

Addiction to morphine is a chronic brain disease leading to compulsive abuse. Drug addiction animal models with and without conditioned place preference (CPP) training have been used to investigate cue-elicited drug craving. We used 18 F-fluorodeoxyglucose (18 F-FDG) and 11 C-2-ß-carbomethoxy-3-ß-(4-fluorophenyl)tropane (11 C-CFT) micro-PET/CT scans to examine the regional changes in brain glucose metabolism and dopamine transporter (DAT) availability to study their relationship underlying drug memory in morphine-treated rat models with and without CPP. Standardized uptake value ratio (SUVr) of 18 F-FDG significantly decreased in the medial prefrontal cortex (mPFC) and cingulate with short-term morphine administration compared with the baseline condition. Voxelwise analysis indicated glucose metabolism alterations in the somatosensory cortex, hippocampus and cingulate in morphine-treated rats and in the striatum, thalamus, medial prefrontal cortex, primary motor cortex and many regions in the cortex in the CPP group compared with the baseline condition. Alterative glucose metabolism was also observed in the striatum, primary somatosensory cortex and some cortical regions in the CPP group compared with morphine alone group. DAT expression alterations were only observed in the long-term morphine compared with the short-term morphine group. This study shows that cerebral glucose metabolism significantly altered during morphine administration and CPP process mainly in the mPFC, striatum and hippocampus, which indicates that the function of these brain regions is involved in cue-induced craving and memory retrieval.

Construction of core-shell Fe3O4@GO-CoPc photo-Fenton catalyst for superior removal of tetracycline: The role of GO in promotion of H2O2 to •OH conversion.

A novel core-shell structured Fe3O4@GO-CoPc magnetic catalyst, which is with magnetite (Fe3O4) as the core, graphene oxide (GO) as the interlayer and cobalt-phthalocyanine (CoPc) as the shell, was successfully prepared and used as a heterogeneous photo-Fenton catalyst for tetracycline (TC) degradation in this work. The core-shell structure of the catalyst was confirmed by XRD, FTIR, SEM and TEM. BET and magnetic hysteresis loops measurements indicated that Fe3O4@GO-CoPc catalyst owned large specific surface area and could be easily recovered under an external magnetic field. Meanwhile, the experimental results of TC degradation demonstrated that the photo-Fenton efficiency of Fe3O4@GO-CoPc was excellent. When the reaction time was 120 min, TC could be degraded almost completely in the photo-Fenton system with Fe3O4@GO-CoPc. The high photo-Fenton catalytic activity of Fe3O4@GO-CoPc could be resulted from the effective transfer of photo-generated electrons between CoPc and Fe3O4 by GO. Moreover, the main reaction species, •OH, O2•-, 1O2 and h+, were verified by the analysis of active species in this system. Finally, the mechanism analyses and quantitative analysis results of active species indicated that the introduction of GO accelerated the cycle between Fe(II) and Fe(III) as well as improved the effective utilization of H2O2 (the efficiency of conversion of H2O2 to •OH).

Aging-Related Modular Architectural Reorganization of the Metabolic Brain Network.

Background: Modules in brain network represent groups of brain regions that are collectively involved in one or more cognitive domains. Exploring aging-related reorganization of the brain modular architecture using metabolic brain network could further our understanding about aging-related neuromechanism and neurodegenerations. Materials and Methods: In this study, 432 subjects who performed 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) were enrolled and divided into young and old adult groups, as well as female and male groups. The modular architecture was detected, and the connector and hub nodes were identified to explore the topological role of the brain regions based on the metabolic brain network. Results: This study revealed that human metabolic brain network was modular and could be clustered into three modules. The modular architecture was reorganized from young to old ages with regions related to sensorimotor function clustered into the same module; and the number of connector nodes was reduced and most connector nodes were localized in temporo-occipital areas related to visual and auditory functions in old ages. The major gender difference is that the metabolic brain network was delineated into four modules in old female group with the nodes related to sensorimotor function split into two modules. Discussion: Those findings suggest aging is associated with reorganized brain modular architecture. Clinical Trial Registration number: ChiCTR2000036842. Impact statement Distinguishing the basic biology underlying aging from that underlying disease is critical for the prevention, diagnosis, and treatment of the aging-related brain disorders. In this study, we tried to uncover aging-related brain modular reorganization by using metabolic brain network. We found the modular architecture was slightly reorganized from young to old ages with regions related to sensorimotor function more converged. The number of connector nodes was reduced and most connector nodes were localized into the temporo-occipital regions. The major gender difference was that metabolic brain network was delineated into four modules in the old female group with the sensorimotor functions split into two modules.

Metabolic Brain Network and Surgical Outcome in Temporal Lobe Epilepsy: A Graph Theoretical Study Based on 18F-fluorodeoxyglucose PET.

Drug-resistant temporal lobe epilepsy (TLE) is a potential candidate for surgery; however, nearly one-third subjects had a poor surgical prognosis. We studied the underlying neuromechanism related to the surgical prognosis using graph theory based on metabolic brain network. Sixty-four unilateral TLE subjects with preoperative 18F-fluorodeoxyglucose (FDG) PET scanning were retrospectively enrolled and divided into Ia (Engel class Ia, n = 32) and non-Ia (Engel class Ib-IV, n = 32) groups according to more than 3-year follow-up after unilateral anterior temporal lobectomy (ATL). The metabolic brain network was constructed and the changed metabolic connectivity of Ia and non-Ia was detected compared with 15 matched healthy controls (HCs). Further, the network properties, including small-worldness and global efficiency, were calculated and hub nodes were also identified for the 3 groups respectively. Non-Ia group exhibited increased connectivity between contralateral fusiform gyrus and contralateral lingual gyrus; while Ia showed decreased connectivity mainly among bilateral frontal, temporal and parietal cortex. Graph theoretical analysis revealed that non-Ia group showed increased small-worldness (35%

Nitrogen-Doped Porous Carbon Materials Derived from Graphene Oxide/Melamine Resin Composites for CO2 Adsorption.

CO2 adsorption in porous carbon materials has attracted great interests for alleviating emission of post-combustion CO2. In this work, a novel nitrogen-doped porous carbon material was fabricated by carbonizing the precursor of melamine-resorcinol-formaldehyde resin/graphene oxide (MR/GO) composites with KOH as the activation agent. Detailed characterization results revealed that the fabricated MR(0.25)/GO-500 porous carbon (0.25 represented the amount of GO added in wt.% and 500 denoted activation temperature in °C) had well-defined pore size distribution, high specific surface area (1264 m2·g-1) and high nitrogen content (6.92 wt.%), which was mainly composed of the pyridinic-N and pyrrolic-N species. Batch adsorption experiments demonstrated that the fabricated MR(0.25)/GO-500 porous carbon delivered excellent CO2 adsorption ability of 5.21 mmol·g-1 at 298.15 K and 500 kPa, and such porous carbon also exhibited fast adsorption kinetics, high selectivity of CO2/N2 and good recyclability. With the inherent microstructure features of high surface area and abundant N adsorption sites species, the MR/GO-derived porous carbon materials offer a potentially promising adsorbent for practical CO2 capture.

Single-Step Preparation of Ultrasmall Iron Oxide-Embedded Carbon Nanotubes on Carbon Cloth with Excellent Superhydrophilicity and Enhanced Supercapacitor Performance.

Nanocomposites consisting of carbon materials and metal oxides are generally preferred as anodes in electrochemical energy storage. However, their low capacitance limits the achieved energy density of supercapacitors (SCs) in aqueous electrolytes. Herein, we propose a rapid combustion strategy to construct a novel electrode architecture-ultrasmall Fe2O3 anchoring on carbon nanotubes (FeO-CNT)-as a superhydrophilic and flexible anode for SCs. In 1 M Na2SO4 aqueous electrolyte, such an FeO-CNT-20 anode presents a high capacitance of 483.4 mF cm-2 (326 F g-1) at 1 mA cm-2. The aqueous asymmetric supercapacitor devices (ASCs) assembled by FeO-CNT-20 and MnO2 present a maximum operating potential of 2.0 V with a high areal energy density of 0.11 mWh cm-2 at a power density of 0.5 mW cm-2. The flexible solid-state ASCs display an energy density of 0.99 mWh cm-3 at 14.3 mW cm-3. The rapidly prepared FeO-CNT not only offers an attractive electrode for SCs but also would open up exciting new avenues to the rational design and large-scale preparation of Fe2O3-based nanocomposites for electrochemical energy storage.

N-Doped Porous Carbon Derived from Solvent-Free Synthesis of Cross-Linked Triazine Polymers for Simultaneously Achieving CO2 Capture and Supercapacitors.

It is highly desirable to design advanced heteroatomic doped porous carbon for wide application. Herein, N-doped porous carbon (NPC) was developed via the fabrication of high nitrogen cross-linked triazine polymers followed by pyrolysis and activation with controllable porous structure. The as-synthesized NPC at the pyrolysis temperature of 700 °C possessed rich nitrogen content (up to 11.51 %) and high specific surface area (1353 m2 g-1 ), which led to a high CO2 adsorption capability at 5.67 mmol g-1 at 298.15 K and 5 bar pressure and excellent stability. When the activation temperature was at 600 °C, such NPC exhibited a superior electrochemical performance as anode for supercapacitors with a specific capacitance of 158.8 and 113 F g-1 in 6 M KOH at a current density of 1 and 10 A g-1 , respectively. Notably, it delivered an excellent stability with capacity retention of 97.4 % at 20 A g-1 after 6000 cycles.

A Nomogram Modeling 11C-MET PET/CT and Clinical Features in Glioma Helps Predict IDH Mutation.

Purpose: We developed a 11C-Methionine positron emission tomography/computed tomography (11C-MET PET/CT)-based nomogram model that uses easy-accessible imaging and clinical features to achieve reliable non-invasive isocitrate dehydrogenase (IDH)-mutant prediction with strong clinical translational capability. Methods: One hundred and ten patients with pathologically proven glioma who underwent pretreatment 11C-MET PET/CT were retrospectively reviewed. IDH genotype was determined by IDH1 R132H immunohistochemistry staining. Maximum, mean and peak tumor-to-normal brain tissue (TNRmax, TNRmean, TNRpeak), metabolic tumor volume (MTV), total lesion methionine uptake (TLMU), and standard deviation of SUV (SUVSD) of the lesions on MET PET images were obtained via a dedicated workstation (Siemens. syngo.via). Univariate and multivariate logistic regression models were used to identify the predictive factors for IDH mutation. Nomogram and calibration plots were further performed. Results: In the entire population, TNRmean, TNRmax, TNRpeak, and SUVSD of IDH-mutant glioma patients were significantly lower than these values of IDH wildtype. Receiver operating characteristic (ROC) analysis suggested SUVSD had the best performance for IDH-mutant discrimination (AUC = 0.731, cut-off ≤ 0.29, p < 0.001). All pairs of the 11C-MET PET metrics showed linear associations by Pearson correlation coefficients between 0.228 and 0.986. Multivariate analyses demonstrated that SUVSD (>0.29 vs. ≤ 0.29 OR: 0.053, p = 0.010), dichotomized brain midline structure involvement (no vs. yes OR: 26.52, p = 0.000) and age (≤ 45 vs. >45 years OR: 3.23, p = 0.023), were associated with a higher incidence of IDH mutation. The nomogram modeling showed good discrimination, with a C-statistics of 0.866 (95% CI: 0.796-0.937) and was well-calibrated. Conclusions: 11C-Methionine PET/CT imaging features (SUVSD and the involvement of brain midline structure) can be conveniently used to facilitate the pre-operative prediction of IDH genotype. The nomogram model based on 11C-Methionine PET/CT and clinical age features might be clinically useful in non-invasive IDH mutation status prediction for untreated glioma patients.

Effect of rotenone-induced stress on physiologically active substances in adult Aphis glycines.

The aim of this study was to determine the effect of rotenone stress on Aphis glycines Matsumura (Hemiptera: Aphididae) populations in different habitats of Northeast China. The changes in kinase expression activity of endogenous substances (proteins, total sugars, trehalose, cholesterol, and free amino acids), detoxifying enzymes (cytochrome P450 and glutathione S-transferase), and metabolic enzymes (proteases and phosphofructokinases) in specimens from three populations were compared before and after stress with rotenone at median lethal concentration (LC50) and their response mechanisms were analyzed. Following a 24 h treatment with rotenone, the average LC50 rotenone values in A. glycines specimens from field populations A and B, and a laboratory population were 4.39, 4.61, and 4.03 mg/L, respectively. The degree of changes in the kinase expression activity of endogenous substances also differed, which indicated a difference in the response of A. glycines specimens from varying habitats to LC50 rotenone stress. The content of endogenous substances, detoxifying enzymes, and metabolic enzymes, except for that of free amino acids, changed significantly in all populations treated with rotenone at LC50 compared with that in the control (P < 0.05). The decrease in protein and trehalose content, and the obstruction of cholesterol transportation owing to decreased feeding in stressed individuals were the causes of A. glycines death after rotenone treatment. Aphis glycines resistance to rotenone may be related to cytochrome P450 expression.