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Mood disorders are characterized by great heterogeneity in clinical manifestation. Uncovering such heterogeneity using neuroimaging-based individual biomarkers, clinical behaviors, and genetic risks, might contribute to elucidating the etiology of these diseases and support precision medicine.
Methods
We recruited 174 drug-naïve and drug-free patients with major depressive disorder and bipolar disorder, as well as 404 healthy controls. T1 MRI imaging data, clinical symptoms, and neurocognitive assessments, and genetics were obtained and analyzed. We applied regional gray matter volumes (GMV) and quantile normative modeling to create maturation curves, and then calculated individual deviations to identify subtypes within the patients using hierarchical clustering. We compared the between-subtype differences in GMV deviations, clinical behaviors, cell-specific transcriptomic associations, and polygenic risk scores. We also validated the GMV deviations based subtyping analysis in a replication cohort.
Results
Two subtypes emerged: subtype 1, characterized by increased GMV deviations in the frontal cortex, cognitive impairment, a higher genetic risk for Alzheimer's disease, and transcriptionally associated with Alzheimer's disease pathways, oligodendrocytes, and endothelial cells; and subtype 2, displaying globally decreased GMV deviations, more severe depressive symptoms, increased genetic vulnerability to major depressive disorder and transcriptionally related to microglia and inhibitory neurons. The distinct patterns of GMV deviations in the frontal, cingulate, and primary motor cortices between subtypes were shown to be replicable.
Conclusions
Our current results provide vital links between MRI-derived phenotypes, spatial transcriptome, genetic vulnerability, and clinical manifestation, and uncover the heterogeneity of mood disorders in biological and behavioral terms.
Hepatitis E virus infection is a major cause of acute hepatitis, typically self-limiting but occasionally leading to liver failure. Understanding disease progression factors could inform prevention strategies. This study aimed to analyse the characteristics of a large cohort of hospitalised hepatitis E patients in Tianjin, China, and explore factors influencing their progression to liver failure. A total of 1279 hospitalised patients with hepatitis E were included in this cross-sectional study in Tianjin, China. Student's t-test and the Mann–Whitney U-test were used for comparisons. Multiple logistic regression analysis was used to explore the association. Among these 1279 patients, 107 (8.4%) developed liver failure. Patients with diabetes mellitus (DM) (95% confidence interval [CI] 1.150–2.887, p = 0.011), liver cirrhosis (95% [CI] 2.229–7.224, p < 0.001), and hepatitis B (95% [CI] 1.159–4.512, p = 0.017) were more likely to progress to liver failure. Hepatitis E patients with comorbid DM, liver cirrhosis, or hepatitis B virus co-infection have higher risks of developing liver failure. Hepatitis E vaccination may be recommended for these vulnerable patients to curb disease severity.
Depression is a common mental disorder that endangers physical and mental health. In our study, we aimed to explore whether B vitamins are associated with depression and cognitive dysfunction.
Methods:
We enrolled a total of 220 patients with depression and selected 100 controls at the same time. We determined depression and cognitive impairment by assessments. We recorded the basic parameters of the participants and collected blood samples. In addition, we measured serum levels of B vitamins and brain-derived neurotrophic factor (BDNF).
Results:
We found significant differences in the duration of depression, education, and Hamilton Depression Rating Scale scores between the D-NCI and D-CI groups. We also identified the independent risk factors for patients with depression and cognitive dysfunction. Compared with the healthy controls, serum folate, vitamin B6, and vitamin B12 positively correlated with cognitive dysfunction. The patients with depression and cognitive dysfunction had the lowest levels of B vitamins compared with the other two groups. Our results also showed that the levels of serum folate, vitamin B6, and vitamin B12 in the patients with depression had a positive correlation with each other.
Conclusion:
Our results indicate that vitamin B is associated with depression and cognitive dysfunction and is positively associated with cognitive dysfunction.
Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.
To reduce the seed length while maintaining the advantages of the cuboid KDP-type crystal, a long-seed KDP crystal with size $471~\text{mm}\times 480~\text{mm}\times 400~\text{mm}$ is rapidly grown. With almost the same high cutting efficiency to obtain third harmonic generation oriented samples,this long-seed KDP-type crystal can be grown with a shorter seed than that of the cuboid KDP-type crystal. The full width at half maximum of the high-resolution X-ray diffraction of the (200) crystalline face is 28.8 arc seconds, indicating that the long-seed KDP crystal has good crystalline quality. In the wavelength range of 377–1022 nm, the transmittance of the long-seed KDP crystal is higher than 90%. The fluence for the 50% probability of laser-induced damage (LID)is $18.5~\text{J}/\text{cm}^{2}$ (3 ns, 355 nm). Several test points survive when the laser fluence exceeds $30~\text{J}/\text{cm}^{2}$ (3 ns, 355 nm), indicating the good LID performance of the long-seed KDP crystal. At present, the growth of a long-seed DKDP crystal is under way.
Human milk fat is specially tailored to supply the developing infant with adequate and balanced nutrients. The present study aimed to quantify the composition of fatty acids, tocopherols and carotenoids in human milk, with special emphasis on the lactational changes. Colostrum, transitional and mature milk samples were collected longitudinally from the same forty-two healthy, well-nourished Chinese mothers. Fatty acids were quantified by GC with carotenoids (carotenes and xanthophylls) and tocopherols (α-, γ-tocopherol) determined by HPLC. Total fatty acid (TFA) content increased from 15·09 g/l in colostrum to 32·57 g/l in mature milk with the percentages of DHA and arachidonic acid (ARA) decreased. The ratio of n-6:n-3 PUFA and ARA:DHA remained constant during lactation at about 11:1 and 1·3:1, respectively. Both α-tocopherol and γ-tocopherol decreased over lactation with the ratio of α-:γ-tocopherol declined significantly from 7·21:1 to 4·21:1 (P < 0·001). Carotenoids all dropped from colostrum to mature milk as the less polar carotenes dropped by 88·67 %, while xanthophylls only dropped by 35·92 %. Lutein was predominated in both transitional and mature milk carotenoids (51·64–52·49 %), while colostrum carotenoids were mainly composed of lycopene (32·83 %) and β-carotene (30·78 %). The concentrations of tocopherols and xanthophylls but not carotenes were positively associated with TFA content in milk. These results suggested that colostrum and mature milk contained divergent lipid profiles and selective transfer mechanisms related to polarity might be involved. The present outcomes provide new insights for future breast-feeding studies, which also add in scientific evidences for the design of both initial and follow-on infant formulas.
In this study, a new ultra-wideband (UWB) band-edge selectivity antenna with a modified radiation slot using defected ground structure (DGS) is presented to obtain bandpass filtering reflection coefficient and gain performance. The well-designed DGS is designed on backside metallic of the substrate and can be seen as a low-pass filter that provides a good roll-off at a higher frequency. By connecting the DGS and the stepped slot and making them merge with each other, good cut-off property in the upper passband and better in-band impedance characteristics are obtained. Measured results show that the proposed design not only shows good band-edge selectivity in reflection coefficient and gain performance but also has a good impedance matching of −13.5 dB reflection coefficients and a good radiation efficiency of 90% in the operating frequencies. The measured bandwidth defined with the reflection coefficient less than −10 dB is from 3.1–11.2 GHz. Furthermore, the size of the filtering UWB antenna is 22 mm × 12 mm, which is smaller than many individual UWB antennas and UWB filters.
A compact reconfigurable filtering ultra-wideband (UWB) antenna with switchable band-notched functions is proposed. The basic structure of the proposed design is a filtering slot antenna with good band-edge selectivity using stepped impedance resonator feeding line. The reconfigurability is achieved by using two microstrip lines paralleling to the feeding line and two PIN diodes. The reconfigurable structure and bias circuit of the antenna are relatively simple and are not connected to the radiation structure, so they have little negative influence on the radiation characteristics of the antenna. Total four states could be achieved by using two PIN diodes to short the microstrip lines and ground. To verify the performance of the final design, multiple measured and simulated results in frequency and time domain are studied and analyzed. The measured results agreed very well with simulation. Compared with the traditional UWB antenna, the proposed antenna has advantages in size, filtering function in-band and out-of-band, and tunable states for multiple UWB applications.
The granitic rocks of the Tarim large igneous province (LIP) are temporally and spatially related to mafic intrusions. However, their tectonic setting and genetic relationship are debated. Here, we report geochemical, and zircon U–Pb–Hf isotopic results for three alkali feldspar granitic plutons in the Halajun area, western margin of the Tarim Block. Zircon U–Pb ages suggest these plutons were emplaced at 268–275 Ma, coeval with the neighbouring mafic–ultramafic complexes and syenitic rocks. These granitic rocks have high contents of SiO2, alkalis, Rb, Th, Zr and REE (except Eu), and high ratios of FeO*/MgO and Ga/Al, and show strong depletions in Ba, Sr, Eu, which are commonly observed in the A1-type granites. Zircon Hf isotopes reveal a limited range of εHf(t) values from −1.0 to +3.5 for different samples from three granitic plutons, obviously higher than those (mostly <0) of the mafic rocks. This distinct difference, along with a Daly gap and small volume of mafic rocks, argues against extreme fractionation of mafic magma as the main origin of the A1-type granites. Instead the A1-type granites were most likely derived from partial melting of newly underplated rocks triggered by the upwelling asthenosphere, followed by extensive fractionation. These A1-type granites were emplaced within an anorogenic setting during the late stage of the Tarim LIP, which possibly lasts for more than 30 Ma. The Piqiang mafic–ultramafic complex directly stemmed from asthenospheric mantle and Halajun A1-type granites represent two manners of vertical crustal growth.
In this paper, a newnotion of scalar curvature for a Finsler metric $F$ is introduced, and two conformal invariants $Y(M,F)$ and $C(M,F)$ are defined. We prove that there exists a Finsler metric with constant scalar curvature in the conformal class of $F$ if the Cartan torsion of $F$ is sufficiently small and $Y(M,F)C(M,F)<Y({{\mathbb{S}}^{n}})$ where $Y({{\mathbb{S}}^{n}})$ is the Yamabe constant of the standard sphere.
Upon a set of backward orthogonal polynomials, we propose a novel multi-step numerical scheme for solving the decoupled forward-backward stochastic differential equations (FBSDEs). Under Lipschtiz conditions on the coefficients of the FBSDEs, we first get a general error estimate result which implies zero-stability of the proposed scheme, and then we further prove that the convergence rate of the scheme can be of high order for Markovian FBSDEs. Some numerical experiments are presented to demonstrate the accuracy of the proposed multi-step scheme and to numerically verify the theoretical results.
In this paper, a new numerical method for solving the decoupled forward-backward stochastic differential equations (FBSDEs) is proposed based on some specially derived reference equations. We rigorously analyze errors of the proposed method under general situations. Then we present error estimates for each of the specific cases when some classical numerical schemes for solving the forward SDE are taken in the method; in particular, we prove that the proposed method is second-order accurate if used together with the order-2.0 weak Taylor scheme for the SDE. Some examples are also given to numerically demonstrate the accuracy of the proposed method and verify the theoretical results.
Approximately 50 % of patients with inflammatory bowel disease (IBD) suffer from anaemia, with Fe deficiency being the most common cause. CD52 monoclonal antibody (mAb) targets the cell surface CD52 and is effective in depleting lymphocytes through cytolytic effects in vivo. The aim of the present study was to investigate the therapeutic effect of anti-mouse CD52 mAb on Fe-deficient anaemia in IBD. IL-10 knockout mice (IL-10− / −) of 12 weeks with established colitis were treated with anti-mouse CD52 mAb once per week for 2 weeks. Severity of colitis, blood T lymphocytes, blood Hb, haematocrit, plasma erythropoietin (EPO), serum Fe concentration, transferrin saturation, splenic Fe stores, expression of liver hepcidin mRNA, Western blotting of the phosphorylated form of Smad1/5/8 and total Smad1 were measured at the end of the experiment. IL-10− / − mice treated with CD52 mAb showed a reduction in the percentage of CD4+ and CD4+CD45+ T cells in blood and weight loss typically associated with colonic inflammation, serum levels of EPO, the expression of liver hepcidin mRNA and total Smad1 protein, while they showed an increase in Hb concentrations, haematocrit, levels of serum Fe, transferrin saturation and splenic Fe stores. The present results indicated that anti-CD52 therapy may ameliorate Fe-deficient anaemia by reducing colonic inflammation. These findings may open novel horizons in the treatment of patients with IBD by resetting of immunological homeostasis in the gut by depleting the activated T cells in the gut mucosa.
Some families of Randers metrics of scalar flag curvature are studied in this paper. Explicit examples that are neither locally projectively flat nor of isotropic $S$-curvature are given. Certain Randers metrics with Einstein $\alpha $ are considered and proved to be complex. Three dimensional Randers manifolds, with $\alpha $ having constant scalar curvature, are studied.
The redclaw crayfish (Cherax quadricarinatus) is a freshwater crayfishspecies endemic to northern Australia and Papua New Guinea that is the focus of a growingculture industry in number of regions around the world. Here we isolated and characterized15 microsatellite loci from Cherax quadricarinatus and tested variabilityof the loci in 66 unrelated cultured individuals. Thirteen of 15 microsatellite loci werepolymorphic. Number of alleles per locus ranged from two to seven while observed andexpected heterozygosities ranged from 0.172 to 0.985 and from 0.373 to 0.778,respectively. Eleven loci conformed to Hardy–Weinberg equilibrium in the sampledpopulation. These microsatellite loci developed here provide an important resource forstudying genetic diversity and population structure in redclaw crayfish and potentially inother related species.
Lead titanate (PbTiO3) nano- and microtubes were fabricated by wetting ordered porous alumina and macroporous silicon with precursor oligomers coupled with templated thermolysis. The diameters of the PbTiO3 tubes range from a few tens of nanometers up to one micron. The proper selection of the template allowed for a precise adjustment of their size over two orders of magnitude. Electron microscopy and x-ray diffraction revealed that the tube walls were polycrystalline. The generic approach presented here can be adapted for the fabrication of tubes and rods from a multitude of functional inorganic oxides.
Solder joint has been widely used in microelectronics industry as an interconnect of Integrated Circuit (IC) chip and Printed Circuit Board (PCB). Frequently, a functional failure of the component on the system is a result of solder joint damage. Eutectic 63Sn/37Pb solder joint mechanical behaviors on Ni/Au plated copper pad and bare copper pad were experimentally investigated to address the effect of pad surface cleanness on the formation of intermetallic compound. The joints with thinner intermetallic compound layer resulted in a poor solder ball shear strength. Microstructural analysis revealed that the oxidations of Ni and Cu during substrate manufacturing contributed to the improper growth of intermetallic compound during assembly and reliability tests. In additions, the experimental results showed that the growth of the intermetallic compound layer were dependent not only on the time and temperature of solder reflow and testing, but also on the cleanness of the pad surfaces and available area for the diffusion of Ni in the case of Ni/Au plated copper pad, Cu in the case of bare copper pad and Sn in the joint area.
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