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Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.
In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.
Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = −0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.
Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.
To assess the prevalence and to identify the associated factors of malnutrition among elderly Chinese with physical functional dependency.
Face-to-face interviews using standardised questionnaires were conducted to collect demographic information, health-related issues and psychosocial status. Physical function was measured by the Barthel Index (BI), and nutrition status was assessed by the Mini Nutritional Assessment–Short Form. Multivariate binary logistic regression was used to assess associated factors of malnutrition.
A total of 2323 participants (aged ≥ 60 years) with physical functional dependency in five provinces in China were enrolled using a multistage cluster sampling scheme.
The prevalence of malnutrition was 17·9 % (95 % CI 16·3, 19·4). Multivariable binary logistic regression revealed the independent risk factors of poor nutrition status were being female, older age, lower educational status, poor hearing, poor physical functional status, lack of hobbies, low religious participation, poor social support, lack of social participation and changes in social participation. The study found that the most significant independent risk factor for malnutrition was complete physical functional dependence (OR 4·46, 95 % CI 2·92, 6·82).
The findings of the study confirm that malnutrition and the risk of malnutrition are prevalent in Chinese older adults with physical functional dependency. In addition to demographic and physical health-related factors, psychosocial factors, which are often overlooked, are independently associated with nutrition status in Chinese older adults with physical functional dependency. A holistic approach should be adopted to screen for malnutrition and develop health promotion interventions in this vulnerable population.
Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2–3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2–3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.
Maternal one-carbon metabolism during pregnancy is crucial for fetal development and programming by DNA methylation. However, evidence on one-carbon biomarkers other than folate is lacking. We, therefore, investigated whether maternal plasma methyl donors, that is, choline, betaine and methionine, are associated with birth outcomes. Blood samples were obtained from 115 women during gestation (median 26·3 weeks, 90 % range 22·7–33·0 weeks). Plasma choline, betaine, methionine and dimethylglycine were measured using HPLC-tandem MS. Multivariate linear and logistic regression models were used to estimate the association between plasma biomarkers and birth weight, birth length, the risk of small-for-gestational-age and large-for-gestational-age (LGA). Higher level of maternal betaine was associated with lower birth weight (–130·3 (95 % CI –244·8, –15·9) per 1 sd increment for log-transformed betaine). Higher maternal methionine was associated with lower risk of LGA, and adjusted OR, with 95 % CI for 1 sd increase in methionine concentration was 0·44 (95 % CI 0·21, 0·89). Stratified analyses according to infant sex or maternal plasma homocysteine status showed that reduction in birth weight in relation to maternal betaine was only limited to male infants or to who had higher maternal homocysteine status (≥5·1 µmol/l). Higher maternal betaine status was associated with reduced birth weight. Maternal methionine was inversely associated with LGA risk. These findings are needed to be replicated in future larger studies.
Combining density functional theory calculations and temperature programmed desorption (TPD) experiments, the adsorption behavior of various sulfur containing compounds, including C2H5SH, CH3SCH3, tetrahydrothiophene, thiophene, benzothiophene, dibenzothiophene, and their derivatives on the coordinately unsaturated sites of Mo27Sx model nanoparticles, are studied systematically. Sulfur molecules with aromaticity prefer flat adsorption than perpendicular adsorption. The adsorption of nonaromatic molecules is stronger than the perpendicular adsorption of aromatic molecules, but weaker than the flat adsorption of them. With gradual hydrogenation (HYD), the binding affinity in the perpendicular adsorption modes increases, while in flat adsorption modes it increases first, then decreases. Significant steric effects on the adsorption of dimethyldibenzothiophene were revealed in perpendicular adsorption modes. The steric effect, besides weakening adsorption, could also activate the S–C bonds through a compensation effect. Finally, by comparing the theoretical adsorption energies with the TPD results, we suggest that HYD and direct-desulfurization path may happen simultaneously, but on different active sites.
Identifying the relative importance of urban and non-urban land-use types for potential denitrification derived N2O at a regional scale is critical for quantifying the impacts of human activities on nitrous oxide (N2O) emission under changing environments. In this study we used a regional dataset from China including 197 soil samples and six land-use types to evaluate the main predictors (land use, heavy metals, soil pH, soil moisture, substrate availability, functional and broad microbial abundances) of potential denitrification using multivariate and pathway analysis. Our results provide empirical evidence that soils on farms have the greatest potential denitrifying ability (PDA) (10.92±6.08ng N2O-N·g–1 dry soil·min–1) followed by urban soil (6.80±5.35ng N2O-N·g–1 dry soil·min–1). Our models indicate that land use (low vs. high human activity), followed by total nitrogen (TN) and heavy metals (Cu, Zn, Pb, Cd) was the most important driver of PDA. In addition, our path analysis suggests that at least part of the impacts of land use on potential denitrification were mediated via microbial abundance, soil pH and substrates including TN, dissolved organic carbon and nitrate. This study identifies the main predictors of denitrification at a regional scale which is needed to quantify the impact of human activities on ecosystem functionality under changing conditions.
We previously reported four heterozygous missense mutations of MYH7, KCNQ1, MYLK2, and TMEM70 in a single three-generation Chinese family with dual Long QT and hypertrophic cardiomyopathy phenotypes for the first time. However, the clinical course among the family members was various, and the potential myocardial dysfunction has not been investigated.
The objective of this study was to investigate the echocardiographic and electrocardiographic characteristics in a genetic positive Chinese family with hypertrophic cardiomyopathy and further to explore the association between myocardial dysfunction and electric activity, and the identified mutations.
A comprehensive echocardiogram – standard two-dimensional Doppler echocardiography and three-dimensional speckle tracking echocardiography – and electrocardiogram were obtained for members in this family.
As previously reported, four missense mutations – MYH7-H1717Q, KCNQ1-R190W, MYLK2-K324E, and TMEM70-I147T – were identified in this family. The MYH7-H1717Q mutation carriers had significantly increased left ventricular mass indices, elevated E/e’ ratio, deteriorated global longitudinal stain, but enhanced global circumferential and radial strain compared with those in non-mutation patients (all p<0.05). The KCNQ1-R190W carriers showed significantly prolonged QTc intervals, and the MYLK2-K324E mutation carriers showed inverted T-waves (both p<0.05). However, the TMEM70-I147T mutation carriers had similar echocardiography and electrocardiographic data as non-mutation patients.
Three of the identified four mutations had potential pathogenic effects in this family: MYH7-H1717Q was associated with increased left ventricular thickness, elevated left ventricular filling pressure, and altered myocardial deformation; KCNQ1-R190W and MYLK2-K324E mutations were correlated with electrocardiographic abnormalities reflected in long QT phenotype and inverted T-waves, respectively.
The push–pull fatigue characteristics of the peak-aged Mg–0.2Zn–0.5Zr alloys with different addition levels of neodymium (Nd) have been investigated. The fatigue strength (σf) of the Mg–xNd–0.2Zn–0.5Zr (NZx0K) alloy increases proportionally with the increase of the Nd content (CNd) as follows: σf (T6) ≈ (13.8–14.0) CNd + 46 (for x between 0 and 3.0 wt%). The cyclic stress amplitude also increases but the plastic strain value decreases with the increase of the Nd content. The studied alloys exhibit the strain hardening followed by cyclic softening during fatigue test. During the low-cycle fatigue (LCF) test, the cracks originate from the cyclic deformation and cumulative damage. In high-cycle fatigue (HCF), the failure is due to the cyclic deformation and damage irreversibly caused by environment-assisted cyclic slip. The LCF lives of the alloys fitted well with the Coffin–Manson relation and Basquin laws, the three-parameter equation, and the energy-based concepts. The developed multi-scale fatigue (MSF) life models can be used to predict the LCF and HCF lives of the alloys. Among these models, the MSF life can well capture the influence of Nd addition on fatigue.
The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the β-myosin heavy chain. Neither the proband’s father nor the mother were carriers of this sequence variant; thus, the mutation was classified as “de novo”. Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.
Unawareness of deficits is common and is associated with poor outcomes in Alzheimer's disease (AD); however, little is known about correlated neurobiochemical changes.
Proton magnetic resonance spectroscopy was used to examine neurobiochemical correlates of unawareness of deficits as assessed by the Dementia Deficit Scale in 36 patients with AD. Magnetic resonance spectroscopy spectra were acquired from the anterior cingulate area and right orbitofrontal area. Concentrations of N-acetyl-aspartate (NAA), total creatine, and other neurometabolites were calculated.
Nineteen (52.8%) participants had relative unawareness of deficits. This condition was negatively correlated with NAA/creatine in the anterior cingulate area (β = −0.36, p = 0.025) and positively correlated with NAA/creatine in the right orbitofrontal area (β = 0.41, p = 0.009) after controlling for dementia severity.
These findings suggest unawareness of deficits in AD was associated with the altered neurochemical metabolites in the anterior cingulate area and right orbitofrontal area. However, the two areas might have opposite neuronal functions in unawareness of deficits.
Drug addiction is a major public health issue, yet the underlying adaptation of neural networks by drugs of abuse is not fully understood. We have previously linked chaperone heat shock protein 70 (Hsp70) to drug-induced adaptations. Focusing on the NAc core and shell, the present study aims to provide further findings for our understanding of the relation between behavioural sensitization to morphine and Hsp70 at transcriptional and functional levels in rats. Firstly, we delineated the characteristics of behavioural sensitization induced by a single morphine exposure (1–10 mg/kg, s.c.). Secondly, Hsp70 protein expression in the NAc core was time- and dose-relatedly induced during the development of behavioural sensitization to a single morphine exposure in rats, and Pearson analysis indicated a positive correlation between behavioural sensitization and Hsp70 expression in NAc core. Thirdly, at the transcriptional level, intra-NAc core injection of the specific heat shock factor-I (HSF-I) inhibitor N-Formyl-3,4-methylenedioxy-benzylidine-γ-butyrolactam (KNK437) suppressed Hsp70 expression and the development of behavioural sensitization, while the HSF-I specific inducer geranylgeranylacetone (GGA) promoted both of them. Interestingly, intra-NAc shell injection of KNK437 or GGA did not affect the development of behavioural sensitization. Finally, both the functional inhibition of Hsp70 ATPase activity by methylene blue (MB), and the antagonism of Hsp70 substrate binding site (SBD) activity by pifithrin-μ (PES) impaired the development of behavioural sensitization when they were microinjected into the NAc core. Taken together, the critical involvement of chaperone Hsp70 in behavioural sensitization to morphine identifies a biological target for long-lasting adaptations with relevance to addiction.
In this paper, an extremal eigenvalue problem to the Sturm-Liouville equations with discontinuous coefficients and volume constraint is investigated. Liouville transformation is applied to change the problem into an equivalent minimization problem. Finite element method is proposed and the convergence for the finite element solution is established. A monotonic decreasing algorithm is presented to solve the extremal eigenvalue problem. A global convergence for the algorithm in the continuous case is proved. A few numerical results are given to depict the efficiency of the method.
A fully higher-order compact (HOC) finite difference scheme on the 9-point two-dimensional (2D) stencil is formulated for solving the steady-state laminar mixed convection flow in a lid-driven inclined square enclosure filled with water-Al2O3 nanofluid. Two cases are considered depending on the direction of temperature gradient imposed (Case I, top and bottom; Case II, left and right). The developed equations are given in terms of the stream function-vorticity formulation and are non-dimensionalized and then solved numerically by a fourth-order accurate compact finite difference method. Unlike other compact solution procedure in literature for this physical configuration, the present method is fully compact and fully higher-order accurate. The fluid flow, heat transfer and heat transport characteristics were illustrated by streamlines, isotherms and averaged Nusselt number. Comparisons with previously published work are performed and found to be in excellent agreement. A parametric study is conducted and a set of graphical results is presented and discussed to elucidate that significant heat transfer enhancement can be obtained due to the presence of nanoparticles and that this is accentuated by inclination of the enclosure at moderate and large Richardson numbers.
De-novo protein synthesis is required in the development of behavioural sensitization. A prior screening test from our laboratory has implicated heat shock protein 70 (Hsp70) as one of the proteins required in this behavioural plasticity. Thus, this study was designed to extend our understanding of the role of Hsp70 in the development of behavioural sensitization induced by a single morphine exposure in mice. First, by employing transcription inhibitor actinomycin D (AD) and protein synthesis inhibitor cycloheximide (CHX), we identified a protein synthesis-dependent labile phase (within 4 h after the first morphine injection) in the development of behavioural sensitization to a single morphine exposure. Second, Hsp70 protein expression in the nucleus accumbens correlated positively with locomotor responses of sensitized mice and, more importantly, the expression of Hsp70 increased within 1 h after the first morphine injection. Third, AD and CHX both prevented expression of Hsp70 and disrupted the development of the single morphine induced behavioural sensitization, which further implied Hsp70 was highly associated with behavioural sensitization. Finally, the selective Hsp70 inhibitor pifithrin-μ (PES) i.c.v. injected in mice prevented the development of behavioural sensitization and, critically, this inhibitory effect occurred only when PES was given within 1 h after the first morphine injection, which was within the labile phase of the development period. Taken together, we draw the conclusion that Hsp70 is crucially involved in the labile phase of the development of behavioural sensitization induced by a single morphine exposure, probably functioning as a molecular chaperone.
The Chinese Area Positioning System (CAPS) is a regional satellite navigation system; its space segment consists of some Geostationary Earth Orbit (GEO) satellites and 2∼3 Inclined Geo-Synchronous Orbit (IGSO) satellites. Only a few satellites are needed to provide good area coverage and hence it is an ideal space segment for a regional navigation system. A time transfer mode is used to transmit navigation signals, so no high-precision atomic clocks are required onboard the satellites; all of the transferred navigation signals are generated by the same atomic clock at the master control station on the ground. By using virtual clock technology, the time of emission of signals from the ground control station is transformed to the time of transfer of signals at the phase centre of the satellite antenna; thus the impact of ephemeris errors of satellite on positioning accuracy is greatly decreased, enabling the CAPS to have the capability of wide area augmentation. A novel technology of orbit determination, called Paired Observation Combination for Both Stations (POCBS), proposed by the National Time Service Centre, is used in CAPS. The generation and measurement of ranging signals for the orbit survey are carried out in the ground station and the instrument errors are corrected in real-time. The determination of the clock offset is completely independent of the determination of satellite orbit, so the error of the clock offset has no impact on orbit determination. Therefore, a very high precision of satellite orbits, better than 4·2 cm (1 drms) can be obtained by the stations under regional distribution.
Corticotropin-releasing hormone (CRH) is considered the driving force of the hypothalamo-pituitary-adrenal (HPA) axis and plays an important role in mood regulation. The HPA axis is reported to be closely related to acute stress-induced tau phosphorylation in the rodent hippocampus. However, the relationship between the hyperactive HPA axis and tau phosphorylation in the hippocampus and hence the functional implications for chronic stress are not fully understood. In this study, we aimed to examine tau phosphorylation and the effect on axonal transport of mitochondria in the hippocampus of a chronic stress model. A mouse model was created by neonatal isolation before weaning, followed by chronic mild stress by social isolation after weaning. Behavioural tests showed that the model had a typical depression/anxiety-like behaviour accompanied by increased plasma corticosterone level and hypothalamic CRH mRNA expression. Phosphorylated tau increased significantly, accompanied by increased synaptosomal mitochondrial levels in hippocampus of the chronic stress model. CRH receptor 1 antagonist (CP154,526) treatment, not glucocorticoid receptor antagonist (RU486) treatment, decreased tau phosphorylation and synaptosomal mitochondrial levels in the hippocampus of the mouse model. Consistent with an in-vivo model, when hyperphosphorylated tau was inhibited by lithium in cultured primary hippocampal neurons, mitochondrial transport monitored by live imaging was also decreased. We show here for the first time that phosphorylated tau in the hippocampus of a chronic stress model, accompanied by increased mitochondrial transport, was mediated by CRH receptor 1, not by glucocorticoid receptors, which suggests that centrally derived CRH may be involved in the process of mitochondrial axon transport and hence play an important role in hippocampus of a chronic stress model.
Prophylaxis and treatment with oseltamivir effectively controlled a community outbreak of pandemic influenza A (H1N1) in China. The genetic makeup of strains of different generations seemed to be stable. Travel in confined settings might accelerate the transmission of pandemic influenza in a community outbreak.