Differential Regional Brain Spontaneous Activity in Subgroups of Mild Cognitive Impairment.

Background: Amnestic mild cognitive impairment (aMCI) has a high conversion risk to Alzheimer's disease (AD). The aMCI patients may have only a memory deficit (single-domain-aMCI, sd-aMCI) or deficits in multiple cognitive domains (multiple-domain-aMCI, md-aMCI). However, differences in intrinsic brain activity between these two sub-types remain unclear. Method: Neuropsychological and resting-state functional magnetic resonance imaging (fMRI) data were acquired from 24 patients with sd-aMCI, 23 patients with md-aMCI, and 32 healthy controls (HCs). We used the fractional amplitude of low-frequency fluctuation (fALFF) to characterize the intensity of spontaneous brain activity. The analysis of covariance (ANCOVA) and post hoc tests was performed to determine the between-group differences in fALFF. Results: We found higher fALFF in left-sided superior-to-middle frontal gyri and middle-to-inferior temporal gyri in sd-aMCI compared to both the md-aMCI and HCs. Conversely, a lower fALFF was found in the left inferior parietal lobe in both the md-aMCI and sd-aMCI patients. The fALFF values in the left middle and inferior temporal gyri were correlated with cognitive performances. Conclusion: The gradual reduction in the left inferior parietal lobe from single to multiple domain aMCI suggest a functional inefficiency underlying cognitive impairment, while increased activity in the frontal and temporal gyri in sd-aMCI rather than md-aMCI might indicate functional compensation. This study indicates differential functional profiles in the sd-aMCI and md-aMCI, which may be helpful for the prediction of the future conversion of aMCI to AD.

Complementary iTRAQ Proteomic and Transcriptomic Analyses of Leaves in Tea Plant ( Camellia sinensis L.) with Different Maturity and Regulatory Network of Flavonoid Biosynthesis.

The quality of tea is highly related with the maturity of the fresh tea leaves at harvest. The present study investigated the proteomic and transcriptomic profiles of tea leaves with different maturity, using iTRAQ and RNA-seq technologies. A total of 4455 proteins and 27 930 unigenes were identified, with functional enrichment analyses of GO categorization and KEGG annotation. The compositions of flavonoids (catechins and flavonols) in tea leaves were determined. The total content of flavonoids decreased with leaf maturity, in accordance with the protein regulation patterns of shikimate, phenylpropanoid, and flavonoid pathways. The abundance of ANR had a positive correlation with epi-catechin content, while LAR abundance was positively related with catechin content ( P < 0.05). The biosynthetic network of flavonoid biosynthesis was discussed in combination with photosynthesis, primary metabolism, and transcription factors. Bud had the lowest activities of photosynthesis and carbon fixation but the highest flavonoid biosynthesis ability in opposite to mature leaf. SUS-INV switch might be an important joint for carbon flow shifting into the follow-up biochemical syntheses. This work provided a comprehensive overview on the functional protein profile changes of tea leaves at different growing stages and also proposed a research direction regarding the correlations between primary metabolism and flavonoid biosynthesis.

Altered Default Mode and Sensorimotor Network Connectivity With Striatal Subregions in Primary Insomnia: A Resting-State Multi-Band fMRI Study.

Background: Primary insomnia is a high prevalent sleep disorder. Disturbed brain activity during reward, emotional, and cognitive processing have been observed in insomnia patients. Studies have implicated a critical role of the striatum in these dysfunctions. However, there have been no direct investigations on the whole-brain functional connectivity (FC) of the striatum in insomnia. Methods: We analyzed the group differences in the FC images of 6 predefined striatal subregions based on the multi-band resting-state fMRI data of 18 insomnia patients and 16 healthy controls. Results: We found increased positive FC in the bilateral medial frontal gyrus for bilateral dorsal caudate (DC) and left inferior ventral striatum (VS) subregions, but increased negative FC in the bilateral inferior parietal lobe for the left inferior VSi and right dorsal caudal putamen (DCP) subregions, and in the lateral temporal, occipital, and primary sensorimotor areas for the bilateral DC and left superior VS subregions. The FC between the right DCP and right inferior parietal lobe showed significant positive correlation with Pittsburgh Sleep Quality Index (PSQI). Conclusion: The findings indicate disturbed striatal FC with the default mode network (DMN), the visual and somatosensory areas in insomnia, which likely reflects an inappropriate reward or emotional significance attribute to self-reflection, episodic memory, sensory-perception processes. The altered striatal FC might increase the risk of insomnia patients to develop depression and anxiety.

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment.

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. DATA SOURCES: Using the combined keywords: "RBD", "neurodegenerative disease", "Parkinson disease", and "magnetic resonance imaging", the PubMed/MEDLINE literature search was conducted up to January 1, 2018. STUDY SELECTION: A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. RESULTS: Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. CONCLUSIONS: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases.

Profiling microRNA from Brain by Microarray in a Transgenic Mouse Model of Alzheimer's Disease.

MicroRNAs (miRNAs) are small noncoding RNAs, which regulate numerous cell functions by targeting mRNA for cleavage or translational repression, and have been found to play an important role in Alzheimer's disease (AD). Our study aimed to identify differentially expressed miRNAs in AD brain as a reference of potential therapeutic miRNAs or biomarkers for this disease. We used amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice and age-matched wild-type (WT) littermates to determine the expression of miRNAs in the brain. MiRNAs were profiled by microarray, and differentially expressed miRNAs underwent target prediction and enrichment analysis. Microarray analysis revealed 56 differentially expressed miRNAs in AD mouse brain, which involved 39 miRNAs that were significantly upregulated and 19 that were downregulated at different ages. Among those miRNAs, a total of 11 miRNAs, including miR-342-3p, miR-342-5p, miR-376c-3p, and miR-301b-3p, were not only conserved in human but also predicted to have targets and signaling pathways closely related to the pathology of AD. In conclusion, in this study, differentially expressed miRNAs were identified in AD brain and proposed as biomarkers, which may have the potential to indicate AD progression. Despite being preliminary, these results may aid in investigating pathological hallmarks and identify effective therapeutic targets.

Acute effects of air pollution on enteritis admissions in Xi'an, China.

The correlation between enteritis, a common digestive disease, and exposure to ambient air pollutants has not been examined in a comprehensive manner. The aim of this study was to determine whether an association between short-term air pollution exposure and outpatient visits for enteritis in Xi'an, China, occurred using a time-series investigation. Daily baseline data from January 1, 2013, to December 31, 2015, were obtained. The overdispersed Poisson generalized additive model was used to analyze the association between air pollutant levels and frequency of enteritis. A total of 12,815 outpatient hospital visits for enteritis were identified. A 10-µg/m3 increase in average concentrations of particulate matter (PM)10, PM2.5, nitrogen dioxide (NO2), and sulfur dioxide (SO2), and a 0.1-mg/m3 rise of carbon monoxide (CO) were associated with a significantly elevated number of outpatient visits for enteritis on concurrent days, while ozone (O3) did not markedly affect the frequency of enteritis clinical visits. There were no significant positive effects between two-pollutant and single-pollutant models. Lag models showed that the most prominent responses occurred on concurrent days. Confounding factors of gender and age played a significant role in the observations. Taken together, data indicate that air pollution may result in enhanced occurrence of enteritis attack.

Correction: The Novel Relationship between Urban Air Pollution and Epilepsy: A Time Series Study.

[This corrects the article DOI: 10.1371/journal.pone.0161992.].

The Novel Relationship between Urban Air Pollution and Epilepsy: A Time Series Study.

BACKGROUND AND PURPOSE: The data concerning the association between environmental pollution and epilepsy attacks are limited. The aim of this study was to explore the association between acute air pollution exposure and epilepsy attack. METHODS: A hospital record-based study was carried out in Xi'an, a heavily-polluted metropolis in China. Daily baseline data were obtained. Time-series Poisson regression models were applied to analyze the association between air pollution and epilepsy. RESULTS: A 10 µg/m3 increase of NO2, SO2, and O3 concentrations corresponded to 3.17% (95%Cl: 1.41%, 4.93%), 3.55% (95%Cl: 1.93%, 5.18%), and -0.84% (95%Cl: -1.58%, 0.09%) increase in outpatient-visits for epilepsy on the concurrent days, which were significantly influenced by sex and age. The effects of NO2 and SO2 would be stronger when adjusted for PM2.5. As for O3, a -1.14% (95%Cl: -1.90%, -0.39%) decrease was evidenced when adjusted for NO2. The lag models showed that the most significant effects were evidenced on concurrent days. CONCLUSIONS: We discovered previously undocumented relationships between short-term air pollution exposure and epilepsy: while NO2 and SO2 were positively associated with outpatient-visits of epilepsy, O3 might be associated with reduced risk.

Microbial treatment for prevention and removal of paraffin deposition on the walls of crude pipelines.

Two bacterial strains, paraffin removal strain and biosurfactant-producing strain, named BHJ-1 and QFL-1, were isolated from oil production wells in Daqing oilfield of China. They were subsequently identified as Bacillus cereus QAU68 and Bacillus subtilis XCCX, respectively. As an indicator of the degradation paraffin, the inoculum concentration of BHJ-1 and QFL-1 were added in different proportions, the optimum proportion was 5:2. In this proportion the degradation rate of paraffin could reach 64 %, the prevention rate of paraffin could reach 55 %.

[Clinical and magnetic resonance imaging features of neuromyelitis optics with positive anti-nuclear antibody serum].

OBJECTIVE: To analyze the clinical features and brain, spinal cord magnetic resonance imaging (MRI) features of neuromyelitis optical (NMO) patients with positive anti-nuclear antibody serum (ANAs). METHODS: The clinical data of expanded disability status scale (EDSS) score, duration of the first relieving phase and first year recurrence-positive rate and MRI features of 34 NMO patients at our hospital during the period of 2006-2011 were retrospectively reviewed and divided into two groups according to the outcome of antibodies test:ANAs positive group (n=14) and ANAs negative group (n=20). RESULTS: (1) In the ANAs-positive group, the EDSS score of first NMO attack was (2.8±1.1), first remission continued to (9±9) months and the first year recurrence-positive rate was 71.0%; in the ANAs-negative group, the EDSS score of first NMO attack was 2.3±0.8, first remission continued to (31±39) months and the first year recurrence-positive rate was 30.0%. The differences in the first attack EDSS score, duration of first remission and first recurrence rate between two groups were statistically significant (P<0.05). (2) Brain damage-positive rate in the ANAs-positive group on prompt MRI was 35.71% (5/14) and it was higher than that in ANAs-negative group (5/20). But no significant difference existed between two groups. The spinal cord lesions were predominantly located in cervical and thoracic spinal cords simultaneously in both groups (about 50% respectively). And, in the ANAs-positive group, the cervical lesions involved were much more common than the thoracic counterparts (6/14 vs 1/14). However, in the ANAs-negative group, thoracic segments were usually involved (6/20 vs 4/20). CONCLUSION: With severe neurological deficits in the first clinical attack and a short remission, ANAs-positive NMO patients are more prone to relapse in the first year, brain damage and cervical cord injury.

[A clinical analysis of methylmalonic acidemia in adolescents].

OBJECTIVE: To investigate the clinical characteristics of methylmalonic academia in adolescence cases. METHODS: 4 cases were diagnosed methylmalonic academia by gas chromatography- mass spectrogram whose clinical, manifestations and treatment process were analyzed. RESULTS: The main clinical manifestations in 4 cases with methylmalonic academia were intellect impairment, epilepsy, pyramid signs; 2 of them suffered with hypoplasia and optic atrophy, one of them suffered with papilledema. Symptoms were improved after treated with cobamamide and L-carnitine in all the 4 cases 1 months later. CONCLUSIONS: The main clinical characteristics of methylmalonic academia in adolescence were intellect impairment, epilepsy and pyramid signs. The symptoms could be improved after treatment.

Equilibrium unfolding mechanism of chicken muscle triose phosphate isomerase.

Triose phosphate isomerase (TIM) was prepared and purified from chicken breast muscle. The equilibrium unfolding of TIM by urea was investigated by following the changes of intrinsic fluorescence and circular dichroism spectroscopy, and the equilibrium thermal unfolding by differential scanning calorimetry (DSC). Results show that the unfolding of TIM in urea is highly cooperative and no folding intermediate was detected in the experimental conditions used. The thermodynamic parameters of TIM during its urea induced unfolding were calculated as DeltaG degrees =3.54 kcal.mol(-1), and m(G) = 0.67 kcal.mol(-1)M(-1), which just reflect the unfolding of dissociated folded monomer to fully unfolded monomer transition, while the dissociation energy of folded dimer to folded monomer is probe silence. DSC results indicate that TIM unfolding follows an irreversible two-state step with a slow aggregation process. The cooperative unfolding ratio, DeltaH(cal)/DeltaH(vH), was measured close to 2, indicating that the two subunits of chicken muscle TIM unfold independently. The van't Hoff enthalpy, DeltaH(vH), was estimated as about 200 kcal.mol(-1). These results support the unfolding mechanism with a folded monomer formation before its tertiary structure and secondary structure unfolding.

Kinetic analysis of ligand-induced autocatalytic reactions.

Protein phosphorylation and limited proteolysis are two most common regulatory mechanisms involving the energy-dependent covalent modification of regulatory enzymes. In addition to modifying other proteins, many protein kinases and proteases catalyse automodification reactions (i.e. reactions in which the kinase or zymogen serves as its own substrate), and their activities are frequently regulated by other regulatory ligands. In the present study, a kinetic analysis of autocatalytic reaction modulated by regulatory ligands is presented. On the basis of the kinetic equation, a novel procedure is developed to evaluate the kinetic parameters of the reaction. As an example of an application of this method, the effects of calcium ions on the autoacatalytic activation of trypsinogen by trypsin is re-examined. The results indicate that the binding affinity for Ca2+-bound trypsinogen to trypsin is at least two orders of magnitude higher than that for Ca2+-free trypsinogen, and therefore that the effect of Ca2+ ions on K(m*) values for trypsinogen is very much greater than that for the model peptides. Based on the experimental results, one possible molecular mechanism has been proposed.

[The characteristics of enhanced gadolinium DTPA brain magnetic resonance images in 298 multiple sclerosis patients].

OBJECTIVE: To investigate the characteristics of enhanced brain magnetic resonance imaging (MRI) with gadolinium-DTPA (GD) in patients with multiple sclerosis (MS). METHODS: Brain enhanced MRI were studied in 186 patients with clinically definite multiple sclerosis. 298 MRI enhanced lesions were followed every 4 weeks and the study lasted 3 months to 2 years. RESULTS: Of the 298 enhanced MRI lesions 207 (69.5%) lasted less than 4 weeks, 251 (84.2%) 8 weeks, and 272 (91.3%) 12 weeks. There were 3 lesions lasting more than 2 years. Round, oval, ring form, arcuate, spotty, or irregular MRI GD enhanced lesions were found in our MS data. CONCLUSIONS: Most of the MRI GD enhanced lesions disappear in 4 weeks. Very few can last more than 2 years. So it is necessary to perform the GD enhanced MRI in 4 weeks for studying MS intracranial GD enhanced lesions. The DA enhanced MRI lesions in MS may be round, oval, ring form, arcuate, spotty or irregular.