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Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD).
In this case–control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities.
In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC.
The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.
Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial.
In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets.
As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated).
These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.
Invasive Tephritid fruit flies are a global threat to both agriculture and horticulture industries. Biosecurity has played a critical role in reducing their damage but becomes more and more challenging after several key chemical pesticides were banned or withdrawn for health or environmental reasons. This has led to non-chemical approaches including heat and cold treatments being broadly utilized to get rid of fruit fly infestation. However, the molecular mechanisms to kill the flies underlying these stressors are not clear yet. This knowledge will certainly help refine current post-harvest treatment strategies and develop more efficient, cost-effective and environmentally friendly approaches for fruit fly management. Previously, the molecular response of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) to heat was examined thoroughly, in which 31 key genes were identified with significant changes in expression levels and their high-resolution expression timeline was constructed across 11 timepoints. However, whether these candidate genes respond to cold in the same way was unknown. Here, a temperature bioassay was conducted and the expression profiles of these genes were investigated across the same 11 timepoints using cold treatment. The results showed that most of candidate genes exhibited divergent expression profiles compared to heat treatment, suggesting that the fly molecular response to cold may be different from those to heat. This study provides new knowledge of Tephritid fruit fly response to cold at a molecular level, which could aid in improving current fruit fly management and facilitate the development of new strategies to control this serious horticultural insect pest.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
To establish optimal gestational weight gain (GWG) in Chinese pregnant women by Chinese-specific BMI categories and compare the new recommendations with the Institute of Medicine (IOM) 2009 guidelines.
Multicentre, prospective cohort study. Unconditional logistic regression analysis was used to evaluate the OR, 95 % CI and the predicted probabilities of adverse pregnancy outcomes. The optimal GWG range was defined as the range that did not exceed a 1 % increase from the lowest predicted probability in each pre-pregnancy BMI group.
From nine cities in mainland China.
A total of 3731 women with singleton pregnancy were recruited from April 2013 to December 2014.
The optimal GWG (ranges) by Chinese-specific BMI was 15·0 (12·8–17·1), 14·2 (12·1–16·4) and 12·6 (10·4–14·9) kg for underweight, normal weight and overweight pregnant women, respectively. Inappropriate GWG was associated with several adverse pregnancy outcomes. Compared with women gaining weight within our proposed recommendations, women with excessive GWG had higher risk for macrosomia, large for gestational age and caesarean section, whereas those with inadequate GWG had higher risk for low birth weight, small for gestational age and preterm delivery. The comparison between our proposed recommendations and IOM 2009 guidelines showed that our recommendations were comparable with the IOM 2009 guidelines and could well predict the risk of several adverse pregnancy outcomes.
Inappropriate GWG was associated with higher risk of several adverse pregnancy outcomes. Optimal GWG recommendations proposed in the present study could be applied to Chinese pregnant women.
The present study investigated the influence of berberine (BBR) supplementation in normal and high-lipid (HL) diets on lipid metabolism and accumulation in black sea bream (Acanthopagrus schlegelii). BBR was supplemented at 50 mg/kg to control (Con, 11·1 % crude lipid) and high-lipid (HL, 20·2 % crude lipid) diets and named as ConB and HLB, respectively. After the 8-week feeding trial, fish body length and specific growth rate were significantly reduced by HL diets (P < 0·05). Muscle and whole-body crude lipid contents were significantly influenced by both BBR supplementation and dietary lipid level. Fish fed the HLB diet had significantly lower serum TAG, LDL-cholesterol contents and alanine aminotransferase activity compared with the HL group. The HL group presented vast lipid accumulation in the liver, and hypertrophied hepatocytes along with large lipid droplets, and translocation of nuclear to the cell periphery. These abnormalities in black sea bream were alleviated in the HLB group. BBR supplementation in the HL diet significantly down-regulated the hepatic expression levels of acetyl-CoA carboxylase α, sterol regulatory element-binding protein-1, 6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase and pparγ, whereas the lipoprotein lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1a expression levels were significantly up-regulated. However, the expression levels of these genes showed opposite trends in muscle (except for pparγ). In conclusion, dietary BBR supplementation in the HL diet reduced hepatic lipid accumulation by down-regulating lipogenesis gene expression and up-regulating lipolysis gene expression, and it increased muscle lipid contents with opposite trends of the mechanism observed in the liver.
The razor clam, Sinonovacula constricta, contains high levels of long-chain PUFA (LC-PUFA), which are critical for human health. In addition, S. constricta is the first marine mollusc demonstrated to possess Δ6 fatty acyl desaturase (Fad) and complete LC-PUFA biosynthetic ability, providing a good representative to investigate the molecular mechanism of sterol regulatory element binding proteins (SREBP) in regulating Δ6 Fad for LC-PUFA biosynthesis in marine molluscs. Herein, S. constricta SREBP and Δ6 Fad promoter were cloned and characterised. Subsequently, dual luciferase and electrophoretic mobility shift assays were conducted to explore the SREBP binding elements in the core regulatory region of S. constricta Δ6 Fad promoter. Results showed that S. constricta SREBP had a very conservative basic helix-loop-helix-leucine zipper motif, while S. constricta Δ6 Fad promoter exhibited very poor identity with teleost Fads2 promoters, indicating their differentiation during evolution. A 454 bp region harbouring a core sequence in S. constricta Δ6 Fad promoter was predicted to be essential for the transcriptional activation by SREBP. This was the first report on the regulatory mechanism of LC-PUFA biosynthesis in marine molluscs, which would facilitate optimising the LC-PUFA biosynthetic pathway of bivalves in further studies.
Using a novel database of firm patents and board characteristics across 45 countries, we examine both within- and cross-country determinants of board gender diversity and its relation to corporate innovation. Boards are more likely to include women in countries with narrower gender gaps, higher female labor market participation, and less masculine cultures. Firms with gender diverse boards have more patents and novel patents, and a higher innovative efficiency. Further analyses suggest that gender diverse boards are associated with more failure-tolerant and long-term chief executive officer (CEO) incentives, more innovative corporate cultures, and more diverse inventors, characteristics that are conducive to an improved innovative performance.
This research examines the anger and collective action intentions among different social classes in China. Based on social cognition theory with respect to social class, we proposed that the relationship between group-based anger and collective action intentions would be moderated by social class. To test this hypothesis, two studies were conducted. First, using data collected from a sample of 100 residents of Hubei Province, China, Study 1 found that the relationship between group-based anger and collective action intentions was moderated by social class: group-based anger can predict collective action intentions among the upper social class but not among the lower social class. Then, Study 2 employed a 2 × 2 completely randomised design. Its 118 participants were manipulated to experience a momentary change in their subjective social class and the level of their group-based anger before measuring their collective action intentions. The results were consistent with Study 1. Taken together, the findings suggest that social class does moderate the relationship between group-based anger and collective action intentions.
Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5′UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.
To evaluate the effects of different anthropogenic activities on zooplankton and the pelagic ecosystem, we conducted seasonal cruises in 2010 to assess spatial heterogeneity among the mesozooplankton communities of Xiangshan Bay, a subtropical semi-enclosed bay in China. The evaluation included five different areas: a kelp farm, an oyster farm, a fish farm, the thermal discharge area of a power plant, and an artificial reef, and we aimed to identify whether anthropogenic activities dominated spatial variation in the mesozooplankton communities. The results demonstrated clear spatial heterogeneity among the mesozooplankton communities of the studied areas, dominantly driven by natural hydrographic properties, except in the area near the thermal discharge outlet of the power station. In the outlet area, thermal shock caused by the discharge influenced the mesozooplankton community by decreasing abundance and biomass throughout the four seasons, even causing a shift in the dominant species near the outlet during summer from Acartia pacifica to eurythermal and warm water taxa. Unique features of the mesozooplankton community in the oyster farm may be due to the combined effects of oyster culture and the natural environment in the branch harbour. However, kelp and fish culture, and the construction of an artificial reef did not exert any obvious influence on the mesozooplankton communities up to 2010, probably because of the small scale of the aquaculture and a time lag in the rehabilitation effects of the artificial reef. Thus, our results suggested that the dominant factors influencing spatial variations of mesozooplankton communities in Xiangshan Bay were still the natural hydrographic properties, but the thermal discharge was an anthropogenic activity that changed the pelagic ecosystem, and should be supervised.
A new planar microstrip-fed monopole ultra-wideband (UWB) antenna with dual notched bands has been presented. By employing a simple dual-mode resonator with two symmetrical outer high-impedance lines beside the microstrip feed line of the proposed UWB antenna, two controllable rejection bands with high-frequency selectivity are created. The parametric studies of the proposed structure are explored for the dual band-notched operating mechanism. Finally, the experimental results, including return losses, radiation patterns, and peak gains are shown, declaring that the proposed antenna has good impedance matching performance and radiation pattern properties.
Objective: To study the relationship of Nε-(carboxymethyl)-lysine level (CML)
with microstructure changes of white matter (WM), and cognitive impairment
in patients with type 2 diabetes mellitus (T2DM) and to discuss the
potential mechanism underlying T2DM-associated cognitive impairment. Methods: The study was performed in T2DM patients (n=22) with disease course
≥5 years and age ranging from 65 to 75 years old. A control group consisted
of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of
several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML
levels were measured by enzyme-linked immunosorbent assay, and cognitive
function was assessed by Mini-Mental State Examination and Montreal
cognitive assessment (MoCA). Results: The total Mini-Mental State Examination score in the patient group
(25.72±3.13) was significantly lower than the control group (28.16±2.45)
(p<0.05). In addition, the total MoCA score in the patient group
(22.15±3.56) was significantly lower than the control group 25.63±4.12)
(p<0.01). In the patient group, FA values were significantly decreased in
the corpus callosum, cingulate fasciculus, inferior fronto-occipital
fasciculus, parietal WM, hippocampus, and temporal lobes relative to
corresponding regions of healthy controls (p<0.05). Plasma CML level was
negatively correlated with average FA values in the global brain (r=−0.58,
p<0.01) and MoCA scores (r=−0.47, p<0.05). Conclusions: In T2DM, WM microstructure changes occur in older patients, and
elevations in CML may play a role in the development of cognitive
Results from recent trials assessing the effect of vitamin D supplementation on the prevention of childhood acute respiratory infections (ARI) have been inconsistent. In the present study, we determined whether vitamin D supplementation prevents ARI in healthy children and repeated infections in children with previous ARI. We conducted a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included only randomised controlled clinical trials (RCT) comparing vitamin D supplementation with either placebo or no intervention in children younger than 18 years of age. We identified seven RCT and found that the summary estimates were not statistically significantly associated with a reduction in the risk of ARI (relative risk (RR) 0·79, 95 % CI 0·55, 1·13), all-cause mortality (RR 1·18, 95 % CI 0·71, 1·94), or the rate of hospital admission due to respiratory infection in healthy children (RR 0·95, 95 % CI 0·72, 1·26). However, in children previously diagnosed with asthma, vitamin D supplementation resulted in a 74 % reduction in the risk of asthma exacerbation (RR 0·26, 95 % CI 0·11, 0·59; test of heterogeneity, I2= 0·0 %). Our findings indicate a lack of evidence supporting the routine use of vitamin D supplementation for the prevention of ARI in healthy children; however, they suggest that such supplementation may benefit children previously diagnosed with asthma. Due to the heterogeneity of the included studies and possible publication biases related to this field, these results should be interpreted with caution.
Experimental X-ray powder diffraction data, unit-cell parameters, and space group for niclosamide, C13H8N2O4Cl2, are reported [a = 13.571(1) Å, b = 7.181(8) Å, c = 13.742(3) Å, β = 97.984(7)°, unit-cell volume V = 1326.40 Å3, Z = 4, and space group P21/c]. All measured lines were indexed and are consistent with the P21/c space group. No detectable impurity was observed.
An interesting experimental phenomenon was obtained by Mintz that the hot ductility of an austenitic steel decreases with decreasing strain rate whereas that of a ferritic steel increases. However, the mechanism is still unclear. In this study, the critical time and critical cooling rate of nonequilibrium grain-boundary segregation (NGS) are calculated. It is shown that for Mintz's thermal cycle prior to tensile testing, the effective time of the austenitic steel is shorter than the critical time and that of the ferritic steel is longer than the critical time. When the strain rate decreases, the elastic stress aging time increases. As a result, for the austenitic steel, the grain-boundary segregation of impurity increases, thereby reducing the hot ductility, whereas for the ferritic steel, the segregation of impurity decreases, thereby enhancing the hot ductility. Consequently, the hot ductility loss of both austenitic and ferritic stainless steels is induced by NGS of impurity.
This paper concerns the analytic structure of the self-consistent field theory (SCFT) energy functional of multicomponent block copolymer systems which contain more than two chemically distinct blocks. The SCFT has enjoyed considered success and wide usage in investigation of the complex phase behavior of block copolymers. It is well-known that the physical solutions of the SCFT equations are saddle points, however, the analytic structure of the SCFT energy functional has received little attention over the years. A recent work by Fredrickson and collaborators [see the monograph by Fredrickson, The Equilibrium Theory of Inhomogeneous Polymers, (2006), pp. 203–209] has analysed the mathematical structure of the field energy functional for polymeric systems, and clarified the index-1 saddle point nature of the problem caused by the incompressible constraint. In this paper, our goals are to draw further attention to multicomponent block copolymers utilizing the Hubbard-Stratonovich transformation used by Fredrickson and co-workers. We firstly show that the saddle point character of the SCFT energy functional of multicomponent block copolymer systems may be high index, not only produced by the incompressible constraint, but also by the Flory-Huggins interaction parameters. Our analysis will be beneficial to many theoretical studies, such as the nucleation theory of ordered phases, the mesoscopic dynamics. As an application, we utilize the discovery to develop the gradient-based iterative schemes to solve the SCFT equations, and illustrate its performance through several numerical experiments taking ABC star triblock copolymers as an example.