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Genome-wide association studies (GWAS) have consistently revealed that a variant of microRNA 137 (MIR137) shows a quite significant association with schizophrenia. Identifying the network of genes regulated by MIR137 could provide insights into the biological processes underlying schizophrenia. In addition, DLPFC functional connectivity, a robust correlate of MIR137, may provide plausible endophenotypes. However, the regulatory role of the MIR137 gene network in the disrupted functional connectivity remains unclear. Here, we tested the effects of the MIR137 regulated genes on the risk for schizophrenia and DLPFC functional connectivity.
To evaluate the additive effects of the MIR137 regulated genes (N = 1274), we calculated a MIR137 polygenic risk score (PRS) for schizophrenia and tested its association with the risk for schizophrenia in the genomic data of a Han Chinese population that included schizophrenia patients (N = 589) and normal controls (N = 575). We then investigated the association between MIR137 PRS and DLPFC functional connectivity in two independent young healthy cohorts (N = 356 and N = 314).
We found that the MIR137 PRS successfully captured the differences in genetic structure between the patients and controls, but the single gene MIR137 did not. We then consistently found that a higher MIR137 PRS was correlated with lower functional connectivities between the DLPFC and both the superior parietal cortex and the inferior temporal cortex in two independent cohorts.
The findings suggested that these two functional connectivities of the DLPFC could be important endophenotypes linking the MIR137-regulated genetic structure to schizophrenia.
This study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarization and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to 3 groups: normal control fed with AIN-93G diet, and 2 sepsis groups provided with either AIN-93G-based diet or identical components except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with cecal ligation and puncture and were sacrificed at 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas interleukin (IL)-4-, and Foxp3-expressing CD4+ T cells percentages were upregulated. Compared to the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells, reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker Kim-1 were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more-balanced blood T helper cell polarization, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects in risk of abdominal infection.
We present studies of the solidification of binary aqueous solutions that undergo time-periodic cooling from below. We develop an experiment for solidification of aqueous
solutions, where the temperature of the cooling boundary is modulated as a simple periodic function of time with independent variations of the modulation amplitude and frequency. The thickness of the mushy layer exhibits oscillations about the background growth obtained for constant cooling. We consider the deviation given by the difference between states with modulated and fixed cooling, which increases when the modulation amplitude increases but decreases with increasing modulation frequency. At early times, the deviation amplitude is consistent with a scaling argument for growth with quasi-steady modulation. In situ measurements of the mush temperature reveal thermal waves propagating through the mushy layer, with amplitude decaying with height within the mushy layer, whilst the phase lag behind the cooling boundary increases with height. This also leads to phase lags in the variation of the mushy-layer thickness compared to the boundary cooling. There is an asymmetry of the deviation of mushy-layer thickness: during a positive modulation (where the boundary temperature increases at the start of a cycle) the peak thickness deviation has a greater magnitude than the troughs in a negative modulation mode (where the boundary temperature decreases at the start of the cycle). A numerical model is formulated to describe mushy-layer growth with constant bulk concentration and turbulent heat transport at the mush–liquid interface driven by compositional convection associated with a finite interfacial solid fraction. The model recovers key features of the experimental results at early times, including the propagation of thermal waves and oscillations in mushy-layer thickness, although tends to overpredict the mean thickness.
We report an experimental study of the distributions of temperature and solid fraction of growing
mushy layers that are subjected to periodical cooling from below, focusing on late-time dynamics where the mushy layer oscillates about an approximate steady state. Temporal evolution of the local temperature
at various heights in the mush demonstrates that the temperature oscillations of the bottom cooling boundary propagate through the mushy layer with phase delays and substantial decay in the amplitude. As the initial concentration
increases, we show that the decay rate of the thermal oscillation with height also decreases, and the propagation speed of the oscillation phase increases. We interpret this as a result of the solid fraction increasing with
, which enhances the thermal conductivity but reduces the specific heat of the mushy layer. We present a new methodology to determine the distribution of solid fraction
in mushy layers for various
, using only measurements of the temperature
. The method is based on the phase behaviour during thermal modulation, and opens up a new approach for inferring mushy-layer properties in geophysical and engineering settings, where direct measurements are challenging. In our experiments, profiles of the solid fraction
exhibit a cliff–ramp–cliff structure with large vertical gradients of
near the mush–liquid interface and also near the bottom boundary, but much more gradual variation in the interior of the mushy layer. Such a profile structure is more pronounced for higher initial concentration
. For very low concentration, the solid fraction appears to be linearly dependent on the height within the mush. The volume-average of the solid fraction, and the local fluctuations in
both increase as
increases. We suggest that the fast increase of
near the bottom boundary is possibly due to diffusive transport of solute away from the bottom boundary and the depletion of solute content near the basal region.
Refugees commonly experience difficulties with emotional processing, such as alexithymia, due to stressful or traumatic experiences. However, the functional connectivity of the amygdala, which is central to emotional processing, has yet to be assessed in refugees. Thus, the present study investigated the resting-state functional connectivity of the amygdala and its association with emotional processing in North Korean (NK) refugees.
This study included 45 NK refugees and 40 native South Koreans (SK). All participants were administered the Toronto Alexithymia Scale (TAS), Beck Depression Inventory (BDI), and Clinician-administered PTSD Scale (CAPS), and differences between NK refugees and native SK in terms of resting-state functional connectivity of the amygdala were assessed. Additionally, the association between the strength of amygdala connectivity and the TAS score was examined.
Resting-state connectivity values from the left amygdala to the bilateral dorsolateral prefrontal cortex (dlPFC) and dorsal anterior cingulate cortex (dACC) were higher in NK refugees than in native SK. Additionally, the strength of connectivity between the left amygdala and right dlPFC was positively associated with TAS score after controlling for the number of traumatic experiences and BDI and CAPS scores.
The present study found that NK refugees exhibited heightened frontal–amygdala connectivity, and that this connectivity was correlated with alexithymia. The present results suggest that increased frontal–amygdala connectivity in refugees may represent frontal down-regulation of the amygdala, which in turn may produce alexithymia.
In situ U–Pb and Hf analyses were used for crustal zircon xenocrysts from Triassic kimberlites exposed in the Rangnim Massif of North Korea to identify components of the basement hidden in the deep crust of the Rangnim Massif and to clarify the crustal evolution of the massif. The U–Pb age spectrum of the zircons has a prominent population at 1.9–1.8 Ga and a lack of Archaean ages. The data indicate that the deep crust and basement beneath the Rangnim Massif are predominantly of Palaeoproterozoic age, consistent with the ages of widely exposed Palaeoproterozoic granitic rocks. In situ zircon Hf isotope data show that most of the Palaeoproterozoic zircon xenocrysts have negative ϵHf(t) values (−9.7 to +0.7) with an average Hf model age of 2.86 ± 0.02 Ga (2σ), which suggests that the Palaeoproterozoic basement was not juvenile but derived from the reworking of Archaean rocks. Considering the existence of Archaean remanent material in the Rangnim Massif and their juvenile features, a strong crustal reworking event is indicated at 1.9–1.8 Ga, during which time the pre-existing Archaean basement was exhausted and replaced by a newly formed Palaeoproterozoic basement. These features suggest that the Rangnim Massif constitutes the eastern extension of the Palaeoproterozoic Liao–Ji Belt of the North China Craton instead of the Archaean Liaonan Block as previously thought. A huge Palaeoproterozoic orogen may exist in the eastern margin of the Sino-Korean Craton.
The present study was undertaken to investigate the antiparasitic activity of extracellular products of Streptomyces albus. Bioactivity-guided isolation of chloroform extracts affording a compound showing potent activity. The structure of the compound was elucidated as salinomycin (SAL) by EI-MS, 1H NMR and 13C NMR. In vitro test showed that SAL has potent anti-parasitic efficacy against theronts of Ichthyophthirius multifiliis with 10 min, 1, 2, 3 and 4 h (effective concentration) EC50 (95% confidence intervals) of 2.12 (2.22–2.02), 1.93 (1.98–1.88), 1.42 (1.47–1.37), 1.35 (1.41–1.31) and 1.11 (1.21–1.01) mg L−1. In vitro antiparasitic assays revealed that SAL could be 100% effective against I. multifiliis encysted tomonts at a concentration of 8.0 mg L−1. In vivo test demonstrated that the number of I. multifiliis trophonts on Erythroculter ilishaeformis treated with SAL was markedly lower than that of control group at 10 days after exposed to theronts (P < 0.05). In the control group, 80% mortality was observed owing to heavy I. multifiliis infection at 10 days. On the other hand, only 30.0% mortality was recorded in the group treated with 8.0 mg L−1 SAL. The median lethal dose (LD50) of SAL for E. ilishaeformis was 32.9 mg L−1.
To investigate the protein-sparing effect of α-lipoic acid (LA), experimental fish (initial body weight: 18·99 (sd 1·82) g) were fed on a 0, 600 or 1200 mg/kg α-LA diet for 56 d, and hepatocytes were treated with 20 μm compound C, the inhibitor of AMP kinase α (AMPKα), treated for 30 min before α-LA treatment for 24 h. LA significantly decreased lipid content of the whole body and other tissues (P<0·05), and it also promoted protein deposition in vivo (P<0·05). Further, dietary LA significantly decreased the TAG content of serum and increased the NEFA content of serum (P<0·05); however, there were no significant differences among all groups in the hepatopancreas and muscle (P>0·05). Consistent with results from the experiment in vitro, LA activated phosphorylation of AMPKα and notably increased the protein content of adipose TAG lipase in intraperitoneal fat, hepatopancreas and muscle in vivo (P<0·05). Meanwhile, LA significantly up-regulated the mRNA expression of genes involved in fatty acid β-oxidation in the same three areas, and LA also obviously down-regulated the mRNA expression of genes involved in amino acid catabolism in muscle (P<0·05). Besides, it was observed that LA significantly activated the mammalian target of rapamycin (mTOR) pathway in muscle of experimental fish (P<0·05). LA could promote lipolysis and fatty acid β-oxidation via increasing energy supply from lipid catabolism, and then, it could economise on the protein from energy production to increase protein deposition in grass carp. Besides, LA might directly promote protein synthesis through activating the mTOR pathway.
Associations between ferritin and insulin sensitivity have been described in recent studies. The possible association showed conflicting results by sex and menopausal status. We aimed to investigate the cross-sectional association of ferritin levels with insulin resistance and β-cell function. A total of 2518 participants (1033 men, 235 pre-menopausal women and 1250 post-menopausal women) were enrolled from the Changfeng Study. A standard interview was conducted, as well as anthropometric measurements and laboratory analyses, for each participant. The serum ferritin level was measured using electrochemiluminescence immunoassay. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. The results showed that the serum ferritin levels were 250·4 (sd 165·2), 94·6 (sd 82·0) and 179·8 (sd 126·6) ng/ml in the men, pre-menopausal and post-menopausal women, respectively. In fully adjusted models (adjusting for age, current smoking, BMI, waist:hip ratio, systolic blood pressure, diastolic blood pressure, TAG, HDL-cholesterol, LDL-cholesterol, log urine albumin:creatinine ratio, leucocytes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase), serum ferritin concentrations are significantly associated with insulin resistance in men and post-menopausal females, and the null association was observed in pre-menopausal females. Interestingly, an increased β-cell function associated with higher ferritin was observed in post-menopausal participants, but not in male participants. In conclusion, these results suggested that elevated serum ferritin levels were associated with surrogate measures of insulin resistance among the middle-aged and elderly male and post-menopausal women, but not in pre-menopausal women.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
An 8-week growth trial was conducted to evaluate the effects of dietary arginine (Arg) levels on growth, gut morphology, oxidation resistance and immunity of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatus♂) juveniles. Seven isoenergetic (1465 kJ (350 kcal)/100-g DM), isoproteic (53·5 % of DM) and isolipidic (7 % of DM) experimental diets were formulated to contain graded Arg levels ranging from 1·9 to 4·7 % (dry weight) at approximately 0·5 % increments. Each diet was randomly assigned to triplicate groups of 16 juvenile fish (average initial body weight: 11·7 (sd 0·1) g) and was administered twice daily (08.00 and 16.00 hours). After the growth trial, all remaining fish were fed their prescribed diets for 2 d and then exposed to 4·5 mg Cu2+/l water for 36 h. Results showed that growth performance and feed utilisation of experimental fish were significantly affected by different dietary Arg levels. Weight gain % (WG%) of fish was increased as dietary Arg increased, reaching a peak value at 3·8 % dietary Arg level, and when dietary Arg level increased to 4·7 % WG% was reduced. Fish fed 1·9 and 2·2 % dietary Arg levels had higher daily feed intake compared with fish fed other dietary Arg levels. Feed conversion ratios in fish fed 1·9, 2·2, 2·7 and 4·7 % dietary Arg levels were higher than those in fish fed 3·1, 3·8 and 4·1 % dietary Arg levels. Protein efficiency ratio and protein productive value (PPV) increased with an increase in dietary Arg, up to a peak value at 3·8 % dietary Arg level, above which these parameters declined. On the basis of quadratic regression analysis of weight gain % (WG%) or PPV against dietary Arg levels, the optimal dietary Arg requirement for hybrid grouper was estimated to be 3·65 %. Fish fed 3·8 % dietary Arg had higher whole-body and muscle protein contents compared with fish fed other dietary Arg levels. Fish fed 3·8 and 4·1 % dietary Arg levels had higher levels of mRNA for insulin-like growth factor-I and target of rapamycin in the liver compared with fish fed other dietary Arg levels. Hepatic S6 kinase 1 mRNA expression in fish fed 3·8 % dietary Arg level was higher than that in fish fed any of the other dietary Arg levels. Gut morphology, hepatic antioxidant indices and immune indices in serum and head kidney were significantly influenced by dietary Arg levels. In conclusion, the optimal dietary Arg requirement for hybrid grouper was estimated to be 3·65 %, and suitable dietary Arg supplementations improved gut morphology and oxidation resistance of hybrid grouper.
In traditional East Asian medicine, cold–heat patterns have been widely used in the diagnosis and treatment of patients suffering from various diseases. The present study aimed to estimate the heritability of cold–heat patterns. Trained interviewers administered a cold–heat pattern questionnaire to 1,753 twins (mean age = 19.1 ± 3.1 years) recruited throughout South Korea. Correlations for the cold pattern (CP) were 0.42 (95% CI [0.28, 0.54]) for monozygotic (MZ) males, 0.16 (95% CI [-0.08, 0.39]) for dizygotic (DZ) males, 0.40 (95% CI [0.30, 0.49]) for MZ females, 0.30 (95% CI [0.12, 0.45]) for DZ females, and 0.07 (95% CI [-0.11, 0.25]) for opposite-sex DZ twins. The corresponding twin correlations for the heat pattern (HP) were 0.38 (95% CI [0.24, 0.51]), -0.22 (95% CI [-0.43, 0.02]), 0.34 (95% CI [0.24, 0.43]), 0.21 (95% CI [0.03, 0.37]), and 0.08 (95% CI [-0.10, 0.26]), respectively. These patterns of twin correlations suggested significant genetic effects on the HP and the CP. Model-fitting analysis revealed that heritability estimates in both sexes were 40% (95% CI [38, 42]) for the CP and 33% (95% CI [25, 42]) for the HP, with the remaining variances attributable to unique environmental variances. These estimates did not vary significantly with age during adolescence and young adulthood.
Tomographic particle image velocimetry (TPIV) measurement with six high-resolution charge-coupled device (CCD) cameras is conducted to investigate flow structures over a finite circular cylinder with an aspect ratio of 2 (
). This short wall-mounted cylinder is fully immersed in a thick turbulent boundary layer (
). Focus is placed on the three-dimensional instantaneous vortex structures and their dynamic characteristics in the wake flow fields. Based on the present results, a refined topological model of the mean wake field behind the finite circular cylinder is proposed, where the spatial locations of the typical vortex structures and their interactions are described in more detail. Among the reported typical vortex structures (i.e. the horseshoe, tip, base, trailing and arch vortex), emphasis is laid on discussion of the tip and arch vortex. The instantaneous 3D M-shape arch vortex and an alternating large-scale streamwise vortex are first found in the present experiment, and their developments are also discussed. Therefore, it is suggested that the instantaneous finite-cylinder wake is dominated by the arch vortex system and the large-scale streamwise vortices. Moreover, in the instantaneous volumetric flow fields, both the antisymmetric and the symmetric wake behaviours are observed. With proper orthogonal decomposition (POD) analysis, the dynamic characteristics of the wake field are clarified. Different from the flow around an infinite cylinder without control, the third and fourth POD modes are characterized by low-frequency symmetric shedding. The low-frequency feature shown in the second mode pair is observed and associated with the occurrence of instantaneous symmetric 3D wake behaviour triggered by the low-aspect-ratio effect and the extension of the separated shear layer. The low frequency seems be attributed to the flapping phenomenon, i.e. oscillation of the recirculation in the backward-facing step flow. It is found that the flapping motion has a modulating effect on the occurrence of the antisymmetric shedding vortex and thus the large-scale streamwise vortex.
Our aim was to examine the prevalence, correlates, and association of depressive and anxiety disorders with quality of life (QoL) and such other outcomes as the need for psychosocial services in cancer patients.
A total of 400 patients participated in a multicenter survey involving five cancer centers located throughout Korea. The Short-Form Health Survey, the MD Anderson Symptom Inventory, the Mini-Mental Adjustment to Cancer (MINI-MAC), and Mini-International Neuropsychiatric Interview were administered.
The prevalence rates for depressive and anxiety disorders were 16 and 17.1%, respectively. Younger age and poor Eastern Cooperative Oncology Group performance status, and all physical symptoms, as well as helplessness/hopelessness, anxious preoccupation (AP), and cognitive avoidance (CA) on the MINI-MAC were found to be significantly related to depressive disorder (DD) in a univariate logistic regression analysis. Metastases, the symptoms of disturbed sleep, dry mouth, and numbness or tingling, as well as AP and CA were significantly correlated with anxiety disorder (AD) in the univariate analysis. In the multivariate analyses, only AP was significant for AD (odds ratio = 2.94, p < 0.001), while none reached statistical significance for DD. Psychiatric comorbidity status had a detrimental effect on various dimensions of QoL. Patients with DD or AD reported a significantly higher need for professional psychosocial services.
Significance of results:
Given the substantial prevalence and pervasive impact of DD and AD on various aspects of QoL, its assessment and care should be integrated as a regular part of oncological care throughout the cancer continuum.
To investigate lung function in Chinese patients suffering from chronic rhinosinusitis with nasal polyps and examine its association with histopathological features.
The lung function of 99 patients with nasal polyps was measured. Haematoxylin and eosin and immunohistochemistry staining were performed to evaluate any inflammatory cells and epithelial tissue remodelling.
Predicted maximal expiratory flow rate at 25 per cent vital capacity was reduced (p < 0.05) in epithelial hyperplasia, and predicted maximal expiratory flow rate at 50 per cent vital capacity was reduced (p < 0.05) in goblet cell hyperplasia. Both peripheral blood eosinophilia and tissue eosinophilia nasal polyps manifested significantly reduced: forced expiratory volume in 1 second/forced vital capacity ratio, predicted maximal expiratory flow rate at 25, 50 and 75 per cent of vital capacity, and predicted maximal mid-expiratory flow. Peripheral blood eosinophils were negatively correlated with predicted maximal expiratory flow rate at 25 and 50 per cent of vital capacity, and predicted maximal mid-expiratory flow. Eosinophils in tissue were negatively correlated with all lung function parameters investigated except predicted forced vital capacity.
Clinicians should be aware of lung function decline in nasal polyps patients, especially in those with tissue eosinophilia.
This research was designed for the first time to investigate the photocatalytic activities of MoO3/g-C3N4 composite in converting CO2 to fuels under simulated sunlight irradiation. The composite was synthesized using a simple impregnation-heating method and MoO3 nanoparticles was in situ decorated on the g-C3N4 sheet. Characterization results indicated that the introduction of MoO3 nanoparticles into g-C3N4 fabricated a direct Z-scheme heterojunction structure. The effective interfacial charge-transfer across the heterojunction significantly promoted the separation efficiency of charge carriers. The optimal CO2 conversion rate of the composite reached 25.6 μmol/(h gcat), which was 2.7 times higher than that of g-C3N4. Additionally, the synthesized MoO3/g-C3N4 also presented excellent photoactivity in RhB degradation under visible-light irradiation.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P < 0.05). The blastocyst formation rate was higher in the group treated with AZD5438 for 4 h than in the groups treated with AZD5438 for 2 or 6 h (42.8% vs. 38.6% and 37.2%, respectively; P > 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.