Highly Active Manganese Oxide from Electrolytic Manganese Anode Slime for Efficient Removal of Antibiotics Induced by Dissociation of Peroxymonosulfate.

In this paper, high-activity manganese oxide was prepared from electrolytic manganese anode slime to realize the efficient removal of antibiotics. The effects of sulfuric acid concentration, ethanol dosage, liquid-solid ratio, leaching temperature and leaching time on the leaching of manganese from electrolytic manganese anode slime were systematically studied. Under the optimal conditions, the leaching rate of manganese reached 88.74%. In addition, a Mn3O4 catalyst was synthesized and used to activate hydrogen persulfate (PMS) to degrade tetracycline hydrochloride (TCH). The synthesized Mn3O4 was characterized by XRD, XPS, Raman, SEM and HRTEM. As a result, the prepared Mn3O4 is spherical, with high purity and crystallinity. The catalytic activity of Mn3O4 for PMS to degrade TCH was increased to 82.11%. In addition, after four cycles, the performance remained at 78.5%, showing excellent stability and recyclability. In addition, O2- and 1O2 are the main active species in the degradation reaction. The activity of Mn3O4 is attributed to it containing Mn(II) and Mn(III) at the same time, which can quickly realize the transformation of high-valence and low-valence manganese, promote the transfer of electrons and realize the degradation of organic pollutants.

Highly Dispersion Cu2O QDs Decorated Bi2WO6 S-Scheme Heterojunction for Enhanced Photocatalytic Water Oxidation.

Developing suitable photocatalysts for the oxygen evolution reaction (OER) is still a challenging issue for efficient water splitting due to the high requirements to create a significant impact on water splitting reaction kinetics. Herein, n-type Bi2WO6 with flower-like hierarchical structure and p-type Cu2O quantum dots (QDs) are coupled together to construct an efficient S-scheme heterojunction, which could enhance the migration efficiency of photogenerated charge carriers. The electrochemical properties are investigated to explore the transportation features and donor density of charge carriers in the S-scheme heterojunction system. Meanwhile, the as-prepared S-scheme heterojunction presents improved photocatalytic activity towards water oxidation in comparison with the sole Bi2WO6 and Cu2O QDs systems under simulated solar light irradiation. Moreover, the initial O2 evolution rate of the Cu2O QDs/Bi2WO6 heterojunction system is 2.3 and 9.7 fold that of sole Bi2WO6 and Cu2O QDs systems, respectively.

Construction of plasmonic Bi/Bismuth oxycarbonate/Zinc bismuth oxide ternary heterojunction for enhanced charge carrier separation and photocatalytic performances.

In this work, a novel plasmonic ternary Bi/Bismuth oxycarbonate/Zinc bismuth oxide (Bi-Bi2O2CO3-ZnBi2O4) is synthesized synergistically by a one-step hydrothermal method. The results show that the metallic Bi spheres and ZnBi2O4 nanoparticles are uniformly distributed on the surface of flower-like Bi2O2CO3 layer. Compared with the bare ZnBi2O4 and Bi-Bi2O2CO3, the ternary Bi-Bi2O2CO3-ZnBi2O4 heterojunction displays a significantly improved solar energy harvesting efficiency and enhanced photocatalytic degradation activity for environmental organic pollutants. The degradation efficiency of organics reaches to 98.4% under simulated solar light illumination. The degradation kinetics indicates that the photocatalytic reaction rate constant of ternary system is about 4.4 and 29.5 times higher than that of pure ZnBi2O4 and Bi-Bi2O2CO3, respectively. Moreover, O2- and h+ are the main active species in the photodegradation reaction. The improvement of the photocatalytic activity of the composites is attributed to the synergistic effect of ternary heterostructure and surface plasmon resonance (SPR), which promotes charge transfer and effectively inhibits the recombination of photogenerated carriers.

A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function.

Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contribution to behavioral stress, and animals exhibit multiple neuropsychiatric domains. Because the genetics of schizophrenia encompasses diverse proteins that contribute to excitatory synapse plasticity, the identified vulnerability of NPTX2 function can provide a framework for assessing the impact of genetics and the intersection with stress.

VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome.

BACKGROUND: There is an urgent need for objective markers of Alzheimer's disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression, and assess response to disease-modifying therapies. Previously, GluA4 and neuronal pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here, we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. METHODS: We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF biomarkers, CSF Aß42:40 ratio, CSF Aß1-42, CSF p-tau, and CSF NFL. P values were adjusted for multiple testing. RESULTS: In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recall adj.p = .04) and age (adj.p = .0008) and was the best correlate of CSF Aß42:40 (adj.p = .0001), p-tau (adj.p < .0001), and NFL (adj.p < .0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p = .02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4, and Syntaxin-1B all strongly correlated with NPTX2 (p < .0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p < .002). CONCLUSION: These data show proof-of-concept for CSF VAMP-2 as a potential marker of synapse degeneration that correlates with CSF AD and axonal degeneration markers and cognitive performance.

Effects of Ultrasonic Surface Rolling Processing and Subsequent Recovery Treatment on the Wear Resistance of AZ91D Mg Alloy.

AZ91D Mg alloy was treated by ultrasonic surface rolling processing (USRP) and subsequent recovery treatment at different temperatures. The dry sliding friction test was performed to investigate the effects of USRP and subsequent recovery treatment on the wear resistance of AZ91D Mg alloy by a ball-on-plate tribometer. The microstructure, properties of plastic deformation layer and worn morphology were observed by optical microscope (OM), scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) analysis and microhardness tester. Results illustrate that the grains of AZ91D Mg alloy surface layer are refined to nanocrystallines. The maximum microhardness of the top surface of the USRP sample reaches 102.3 HV. When USRP samples are treated by recovery treatment at 150 °C, 200 °C and 250 °C, the microhardness of the top surface decreases to 90.68 HV, 79.29 HV and 75.06 HV, respectively. The friction coefficient (FC) and wear volume loss of the USRP-R-150 sample are the lowest among all the samples. The worn surface morphology of the USRP-R-150 sample is smoother than that of other samples, indicating that the wear resistance of AZ91D Mg alloy treated by USRP and recovery treatment at 150 °C is improved significantly.

Cerebrospinal fluid profile of NPTX2 supports role of Alzheimer's disease-related inhibitory circuit dysfunction in adults with Down syndrome.

BACKGROUND: Alzheimer's disease (AD) is the major cause of death in adults with Down syndrome (DS). There is an urgent need for objective markers of AD in the DS population to improve early diagnosis and monitor disease progression. NPTX2 has recently emerged as a promising cerebrospinal fluid (CSF) biomarker of Alzheimer-related inhibitory circuit dysfunction in sporadic AD patients. The objective of this study was to evaluate NPTX2 in the CSF of adults with DS and to explore the relationship of NPTX2 to CSF levels of the PV interneuron receptor, GluA4, and existing AD biomarkers (CSF and neuroimaging). METHODS: This is a cross-sectional, retrospective study of adults with DS with asymptomatic AD (aDS, n = 49), prodromal AD (pDS, n = 18) and AD dementia (dDS, n = 27). Non-trisomic controls (n = 34) and patients with sporadic AD dementia (sAD, n = 40) were included for comparison. We compared group differences in CSF NPTX2 according to clinical diagnosis and degree of intellectual disability. We determined the relationship of CSF NPTX2 levels to age, cognitive performance (CAMCOG, free and cued selective reminding, semantic verbal fluency), CSF levels of a PV-interneuron marker (GluA4) and core AD biomarkers; CSF Aß1-42, CSF t-tau, cortical atrophy (magnetic resonance imaging) and glucose metabolism ([18F]-fluorodeoxyglucose positron emission tomography). RESULTS: Compared to controls, mean CSF NPTX2 levels were lower in DS at all AD stages; aDS (0.6-fold, adj.p < 0.0001), pDS (0.5-fold, adj.p < 0.0001) and dDS (0.3-fold, adj.p < 0.0001). This reduction was similar to that observed in sporadic AD (0.5-fold, adj.p < 0.0001). CSF NPTX2 levels were not associated with age (p = 0.6), intellectual disability (p = 0.7) or cognitive performance (all p > 0.07). Low CSF NPTX2 levels were associated with low GluA4 in all clinical groups; controls (r2 = 0.2, p = 0.003), adults with DS (r2 = 0.4, p < 0.0001) and sporadic AD (r2 = 0.4, p < 0.0001). In adults with DS, low CSF NPTX2 levels were associated with low CSF Aß1-42 (r2 > 0.3, p < 0.006), low CSF t-tau (r2 > 0.3, p < 0.001), increased cortical atrophy (p < 0.05) and reduced glucose metabolism (p < 0.05). CONCLUSIONS: Low levels of CSF NPTX2, a protein implicated in inhibitory circuit function, is common to sporadic and genetic forms of AD. CSF NPTX2 represents a promising CSF surrogate marker of early AD-related changes in adults with DS.

Identification of novel cerebrospinal fluid biomarker candidates for dementia with Lewy bodies: a proteomic approach.

BACKGROUND: Diagnosis of dementia with Lewy bodies (DLB) is challenging, largely due to a lack of diagnostic tools. Cerebrospinal fluid (CSF) biomarkers have been proven useful in Alzheimer's disease (AD) diagnosis. Here, we aimed to identify novel CSF biomarkers for DLB using a high-throughput proteomic approach. METHODS: We applied liquid chromatography/tandem mass spectrometry with label-free quantification to identify biomarker candidates to individual CSF samples from a well-characterized cohort comprising patients with DLB (n = 20) and controls (n = 20). Validation was performed using (1) the identical proteomic workflow in an independent cohort (n = 30), (2) proteomic data from patients with related neurodegenerative diseases (n = 149) and (3) orthogonal techniques in an extended cohort consisting of DLB patients and controls (n = 76). Additionally, we utilized random forest analysis to identify the subset of candidate markers that best distinguished DLB from all other groups. RESULTS: In total, we identified 1995 proteins. In the discovery cohort, 69 proteins were differentially expressed in DLB compared to controls (p < 0.05). Independent cohort replication confirmed VGF, SCG2, NPTX2, NPTXR, PDYN and PCSK1N as candidate biomarkers for DLB. The downregulation of the candidate biomarkers was somewhat more pronounced in DLB in comparison with related neurodegenerative diseases. Using random forest analysis, we identified a panel of VGF, SCG2 and PDYN to best differentiate between DLB and other clinical groups (accuracy: 0.82 (95%CI: 0.75-0.89)). Moreover, we confirmed the decrease of VGF and NPTX2 in DLB by ELISA and SRM methods. Low CSF levels of all biomarker candidates, except PCSK1N, were associated with more pronounced cognitive decline (0.37 < r < 0.56, all p < 0.01). CONCLUSION: We identified and validated six novel CSF biomarkers for DLB. These biomarkers, particularly when used as a panel, show promise to improve diagnostic accuracy and strengthen the importance of synaptic dysfunction in the pathophysiology of DLB.

Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia.

INTRODUCTION: Synapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD. METHODS: We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses. RESULTS: Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage. DISCUSSION: We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.

Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease.

INTRODUCTION: Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. METHODS: In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. RESULTS: There were 90 normal controls (mean age 73.0, 58% women), 57 MCI (mean age 74.3, 35% women), and 46 AD (mean age 70.7, 41% women). CSF Aß1-42 and Neuronal Pentraxin 2 (NPTX2) were decreased, and CSF Tau, neurogranin, and SNAP25 increased in AD versus controls. Aß1-42/Tau or NPTX2/Tau discriminated AD and controls best. NPTX2/Tau correlated strongly with cognition in AD and MCI and predicted a 2-3-year decline. We replicated findings in the ADNI cohort. DISCUSSION: CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aß1-42 and Tau. This is relevant for prognosis and clinical trials.

Resting-State Functional Connectivity Is Associated With Cerebrospinal Fluid Levels of the Synaptic Protein NPTX2 in Non-demented Older Adults.

Intrinsic functional connectivity of large-scale brain networks has been shown to change with aging and Alzheimer's disease (AD). These alterations are thought to reflect changes in synaptic function, but the underlying biological mechanisms are poorly understood. This study examined whether Neuronal Pentraxin 2 (NPTX2), a synaptic protein that mediates homeostatic strengthening of inhibitory circuits to control cortical excitability, is associated with functional connectivity as measured by resting-state functional magnetic resonance imaging (rsfMRI) in five large-scale cognitive brain networks. In this cross-sectional study, rsfMRI scans were obtained from 130 older individuals (mean age = 69 years) with normal cognition (N = 113) and Mild Cognitive Impairment (N = 17); NPTX2 was measured in the same individuals in cerebrospinal fluid (CSF). Higher levels of NPTX2 in CSF were associated with greater functional connectivity in the salience/ventral attention network, based on linear regression analysis. Moreover, this association was stronger among individuals with lower levels of cognitive reserve, as measured by a composite score (comprised of years of education, reading, and vocabulary measures). Additionally, higher connectivity in the salience/ventral attention network was related to better performance on a composite measure of executive function. Levels of NPTX2 were not associated with connectivity in other networks (executive control, limbic, dorsal attention, and default-mode). Findings also confirmed prior reports that individuals with MCI have lower levels of NPTX2 compared to those with normal cognition. Taken together, the results suggest that NPTX2 mechanisms may play a central role among older individuals in connectivity within the salience/ventral attention network and for cognitive tasks that require modulation of attention and response selection.

Combination of serum microRNAs and ultrasound profile as predictive biomarkers of diagnosis and prognosis for papillary thyroid microcarcinoma.

Circulating microRNAs (miRNAs) are promising diagnostic markers in various types of cancers, including papillary thyroid carcinoma (PTC). However, there is sparse information reported with regards to miRNA expression in papillary thyroid microcarcinoma (PTMC) or concerning the role of a combination of miRNAs and ultrasound (US) in the diagnosis of PTMC before surgery. Therefore, we designed a study that aimed to evaluate miRNA expression levels and their potential associations with US findings and determine whether miRNAs could be used as diagnostic and prognostic biomarkers of PTMC. miR­222, miR­221, miR­146b and miR­21 levels were determined using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) in serum from 58 patients with PTMC and 47 with PTC, 35 patients with benign thyroid nodules (BTN) and 40 control subjects. Expression levels of the four miRNAs in serum were evaluated before and after surgery. The results indicated that miR­222, miR­221, miR­146b and miR­21 expression levels were higher in the PTMC samples than in those from the BTN and control groups and the combination of miRNAs and US had a high sensitivity and specificity for discrimination between BTN and PTMC by receiver operating characteristic (ROC) curve analysis and improved the accuracy of diagnosis of PTMC before surgery. In addition, serum miRNA expression levels were significantly related to poor prognostic factors including metastatic lymph nodules (MLNs), multifocal and bilateral lesions, advanced stage and high­risk PTMC patients. The miRNA expression levels in serum from PTMC patients were rapidly reduced after surgery compared with levels before surgery. In addition, we also analyzed the miRNA expression levels in serum from patients who were divided into two groups according to factors indicating a good or poor prognosis associated with PTMC after surgery. The results suggested that after surgery, the miR­222, miR­146b and miR­21 expression levels were significantly higher in the poor prognosis group compared with these levels in the good prognosis group. Serum miRNA expression levels helped distinguish between benign and malignant nodules and were associated with a poor prognosis in PTMC. Circulating miRNAs may be useful as follow­up biomarkers and as diagnostic and prognostic tools.

Volume-staged Gamma Knife radiosurgery for orbital venous malformations.

OBJECTIVEThis article is a preliminary evaluation of the efficacy of volume-staged Gamma Knife radiosurgery (GKRS) in the treatment of patients with orbital venous malformations (OVMs).METHODSTwenty patients with moderate to large OVMs were treated with volume-staged GKRS between March 2005 and October 2015. The series included 8 male and 12 female patients with an average age of 22.5 years (range 9-45 years). The diagnoses were confirmed intraoperatively and at pathological examination in 14 cases and presumed in accordance with clinical and imaging findings in 6 cases. The median OVM volume was 12.2 cm3 (range 7.1-34.6 cm3). The median interval between stages was 10 months (range 6-12 months). The tumor margin dose for each stage ranged from 11.0 to 13.5 Gy. The median duration of follow-up was 45.5 months (range 18-98 months).RESULTSPeriodically scheduled MRI studies demonstrated evidence of a significant reduction of the original OVM volume in all cases. Visual acuity (VA) was preserved in 18 cases (90%). Five patients (25%) experienced vision improvement of varying degrees, and 13 (65%) experienced long-term preservation of VA at their pre-GKRS level. Deterioration in VA was observed in only 2 cases (10%). MRI demonstrated OVM regression after treatment in all cases, and all patients were found to have reduction of exophthalmos after volume-staged GKRS. Follow-up MRI revealed recurrence in only 1 case (5%). Three patients (15%) developed transient conjunctival edema.CONCLUSIONSThis retrospective investigation indicates that volume-staged GKRS provides an effective management option in selected patients with OVMs, providing excellent visual outcomes. The study adds substantial support for volume-staged GKRS as a major treatment for OVMs.

Surface modification of PGP for a neutrophil-nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein.

Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro-Gly-Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell-nanoparticle delivery system for depression therapy.

Effects of combined radiosurgery and temozolomide therapy on epidermal growth factor receptor and variant III in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly malignant and notably aggressive primary tumour. Variant III of the epidermal growth factor receptor (EGFRvIII) is one of the most common types of variants in GBM, and serves an important role in tumour invasion, proliferation and treatment resistance. In the present study, statistical analyses were performed on data from 57 patients with GBM, and polymerase chain reaction detection was conducted on the tumour tissues from 32 of these patients. The results indicated that the EGFRvIII mutation was significantly associated with tumour malignancy. Human GBMU87-EGFRvIII cell lines were cultured and treated with radiosurgery and temozolomide individually, or with combined radiosurgery and temozolomide treatment. In vitro and in vivo experimental methods were used to detect the expression levels of Ki-67 and EGFRvIII. As verified in the present study, the EGFRvIII mutation is positively correlated with the malignancy of tumours, and combined radiosurgery and temozolomide therapy may inhibit the invasion and proliferation abilities of U87-EGFRvIII more effectively than treatment alone.

Dynamic monitoring of circulating microRNAs as a predictive biomarker for the diagnosis and recurrence of papillary thyroid carcinoma.

Circulating microRNAs (miRNAs/miRs) are considered to be potential biomarkers for numerous types of cancer. However, previous investigations into the expression of miRNAs in the serum of patients with papillary thyroid carcinoma (PTC) to predict diagnosis, prognosis and recurrence have reported conflicting results, and the role of miRNAs remains unclear. The present study dynamically assessed the circulating miRNA profile in patients with PTC and determined whether miRNAs in the serum could be used as biomarkers for the diagnosis, prognosis and recurrence of PTC. The expression levels of 3 reportedly upregulated miRNAs (miR-222, miR-221 and miR-146b) were analyzed using reverse transcription-quantitative polymerase chain reaction in 106 patients with PTC, 35 patients with benign thyroid nodules (BTN) and 40 paired controls. Patients with either newly diagnosed PTC or BTN who were undergoing thyroidectomies were recruited for a dynamic analysis of preoperative and postoperative serum miRNA levels. The results indicated that the expression levels of serum miR-222, miR-221 and miR-146b were significantly increased in patients with newly diagnosed PTC compared with controls and patients with BTN. Receiver operating characteristic curve analysis indicated that these miRNAs had a high diagnostic sensitivity and specificity for PTC prior to surgery. The expression of these three miRNAs in serum was significantly associated with poorer prognostic variables, including extrathyroidal invasion, metastatic lymph nodes and high-risk or advanced tumor node metastasis stage. More notably, the present study identified 2.36-, 2.69- and 5.39-fold reductions in the serum levels of miR-222, miR-221 and miR-146b, respectively, subsequent to patients undergoing a thyroidectomy. In addition, miR-222, miR-221 and miR-146b were overexpressed in the PTC with recurrence group compared with the PTC without recurrence group. Collectively, dynamic monitoring of circulating miRNAs may serve as a non-invasive biomarker for the diagnosis of PTC and the postoperative monitoring of its progression and recurrence.

NPTX2 and cognitive dysfunction in Alzheimer's Disease.

Memory loss in Alzheimer's disease (AD) is attributed to pervasive weakening and loss of synapses. Here, we present findings supporting a special role for excitatory synapses connecting pyramidal neurons of the hippocampus and cortex with fast-spiking parvalbumin (PV) interneurons that control network excitability and rhythmicity. Excitatory synapses on PV interneurons are dependent on the AMPA receptor subunit GluA4, which is regulated by presynaptic expression of the synaptogenic immediate early gene NPTX2 by pyramidal neurons. In a mouse model of AD amyloidosis, Nptx2-/- results in reduced GluA4 expression, disrupted rhythmicity, and increased pyramidal neuron excitability. Postmortem human AD cortex shows profound reductions of NPTX2 and coordinate reductions of GluA4. NPTX2 in human CSF is reduced in subjects with AD and shows robust correlations with cognitive performance and hippocampal volume. These findings implicate failure of adaptive control of pyramidal neuron-PV circuits as a pathophysiological mechanism contributing to cognitive failure in AD.

Fractionated Gamma Knife surgery for giant pituitary adenomas.

OBJECTIVE: To analyze the feasibility and effectiveness of fractionated Gamma Knife surgery (FGKS) for giant pituitary adenomas. METHODS: From June 2005 to May 2016, 14 patients with giant pituitary adenomas were treated with FGKS, and 10 patients (71%) completed follow-up evaluation. All patients had undergone surgical resection at least once prior to FGKS. The median-volume of the adenomas was 17.6cm3(range 4.9-61cm3). RESULTS: The median follow-up period was 31.5 months (range 6-58 months). The size of the tumors decreased in 6 patients and remained stable in 4 patients. The visual acuity improved in 1 patient. None of the patients suffered from vision deterioration caused by FGKS. CONCLUSION: FGKS is an effective treatment modality for giant pituitary adenomas in selected patients.

A LC-MS/MS method for the determination of stachyose in rat plasma and its application to a pharmacokinetic study.

A sensitive, simple and rapid analytical method based on a liquid chromatography-tandem mass spetrometry (LC-MS/MS) has been established and validated for the determination of stachyose in rat plasma. Plasma samples were prepared by protein precipitation with acetonitrile. Separation of stachyose and nystose (internal standard, IS) was achieved using acetonitrile-water (55:45, v/v) as the mobile phase at a flow rate of 1 ml/min for 6 min on an Asahipak NH2P-50 4E column with an Asahipak NH2P-50G 4A guard column. Detection and quantification were conducted by LC-MS/MS method in the negative ion mode using multiple reaction monitoring (MRM) transitions at m/z [M-H](-) 665.4→383.1 for stachyose and 665.5→485.0 for IS, respectively. The method was linear over the concentration ranges of 100-30000 ng/ml with a lower limit of quantification (LLOQ) of 100 ng/ml. The intra- and inter- day precision were all within 8.7% and the accuracy ranged from 97.2-108.4% and 98.3-102.4%, respectively. Stability studies indicated that stachyose was stable under short-term, long-term and three freeze-thaw storage conditions. The method was successfully applied to a pharmacokinetic study involving pulmonary administration of micronized Rehmannia glutinosa oligosaccharides (RGOS) to rats.

Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp.

One of the cardinal features of neural development and adult plasticity is the contribution of activity-dependent signaling pathways. However, the interrelationships between different activity-dependent genes are not well understood. The immediate early gene neuronal-activity-regulated pentraxin (NPTX2 or Narp) encodes a protein that has been associated with excitatory synaptogenesis, AMPA receptor aggregation, and the onset of critical periods. Here, we show that Narp is a direct transcriptional target of brain-derived neurotrophic factor (BDNF), another highly regulated activity-dependent gene involved in synaptic plasticity. Unexpectedly, Narp is bidirectionally regulated by BDNF. Acute BDNF withdrawal results in downregulation of Narp, whereas transcription of Narp is greatly enhanced by BDNF. Furthermore, our results show that BDNF directly regulates Narp to mediate glutamatergic transmission and mossy fiber plasticity. Hence, Narp serves as a significant epistatic target of BDNF to regulate synaptic plasticity during periods of dynamic activity.