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Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear.
Aims
To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age.
Method
The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed.
Results
The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014).
Conclusions
The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.
A new crocodylian, Dongnanosuchus hsui n. gen. n. sp., is described mainly based on four well-preserved skulls from the Eocene Youganwo Formation of the Maoming Basin, southeastern China. It is an alligatoroid and phylogenetically nested within the Orientalosuchina. Dongnanosuchus hsui n. gen. n. sp. differs from all other orientalosuchines primarily in certain features of the skull: (1) a preorbital ridge connects posteriorly with the dorsal orbital rim and a ridge around the anteroventral margin of the orbit, (2) the palatine is short and does not reach the posterior border of the suborbital fenestra, (3) the external mandibular fenestra is closed, and (4) the splenial joins the formation of the mandibular symphysis. The discovery of Dongnanosuchus hsui n. gen. n. sp. confirms the monophyly and North American origin of the Orientalosuchina but suggests that the clade dispersed to Asia via Beringia after diverging from the mainline rather than a sub-lineage of the Alligatoroidea in the Late Cretaceous.
DNA methylation is one of the most important epigenetic modifications in breast cancer (BC) development, and long-term dietary habits can alter DNA methylation. Cadherin-4 (CDH4, a member of the cadherin family) encodes Ca2+-dependent cell–cell adhesion glycoproteins. We conducted a case–control study (380 newly diagnosed BC and 439 cancer-free controls) to explore the relationship of CDH4 methylation in peripheral blood leukocyte DNA (PBL DNA), as well as its combined and interactive effects with dietary factors on BC risk. A case-only study (335 newly diagnosed BC) was conducted to analyse the association between CDH4 methylation in breast tissue DNA and dietary factors. CDH4 methylation was detected using quantitative methylation-specific PCR. Unconditional logistic regressions were used to analyse the association of CDH4 methylation in PBL DNA and BC risk. Cross-over analysis and unconditional logistic regression were used to calculate the combined and interactive effects between CDH4 methylation in PBL DNA and dietary factors in BC. CDH4 hypermethylation was significantly associated with increased BC risk in PBL DNA (ORadjusted (ORadj) = 2·70, (95 % CI 1·90, 3·83), P < 0·001). CDH4 hypermethylation also showed significant combined effects with the consumption of vegetables (ORadj = 4·33, (95 % CI 2·63, 7·10)), allium vegetables (ORadj = 7·00, (95 % CI 4·17, 11·77)), fish (ORadj = 7·92, (95 % CI 3·79, 16·53)), milk (ORadj = 6·30, (95 % CI 3·41, 11·66)), overnight food (ORadj = 4·63, (95 % CI 2·69, 7·99)), pork (ORadj = 5·59, (95 % CI 2·94, 10·62)) and physical activity (ORadj = 4·72, (95 % CI 2·87, 7·76)). Moreover, consuming milk was significantly related with decreased risk of CDH4 methylation (OR = 0·61, (95 % CI 0·38, 0·99)) in breast tissue. Our findings may provide direct guidance on the dietary intake for specific methylated carriers to decrease their risk for developing BC.
To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows’ diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1–PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.
Topological quantum materials are a class of compounds featuring electronic band structures, which are topologically distinct from common metals and insulators. These materials have emerged as exceptionally fertile ground for materials science research. The topologically nontrivial electronic structures of these materials support many interesting properties, ranging from the topologically protected states, manifesting as high mobility and spin-momentum locking, to various quantum Hall effects, axionic physics, and Majorana modes. In this article, we describe different topological matters, including topological insulators, Weyl semimetals, twisted graphene, and related two-dimensional Chern magnetic insulators, as well as their heterostructures. We focus on recent materials discoveries and experimental advancements of topological materials, and their heterostructures. Finally, we conclude with prospects for the discovery of additional topological materials for studying quantum processes, quasiparticles and their composites, as well as exploiting potential applications of these materials.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
3D ordered bimodal mesoporous carbon (OBMC) with a high specific surface area of 1368.7 m2/g, ordered large mesopores, and small mesopores on the walls is prepared by a surfactant-free rapid method using SiO2 nanosphere arrays as templates. The resulting OBMC is then composited with sulfur to prepare S/OBMC hybrids via a simple solution infiltration method followed by a heat treatment process. In S/OBMC composite, sulfur is uniformly infiltrated inside the 3D hierarchical pores of OBMC. On the basis of this systematic design, the obtained S/OBMC cathode shows a large discharge capacity value of 1590 mA h/g at first cycle and maintains 989 mA h/g after 100 cycles at 0.2 C. Furthermore, at 1 C charge–discharge rate, a reversible discharge capacity of 733 mA h/g after 100 cycles is reached. The extraordinary electrochemical property of S/OBMC derives from the unique bimodal mesoporous structure with large mesopores and small mesopores that can facilitate the mass transfer and strict dissolution of polysulfide species into the electrolyte.
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.
We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60–<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.
Maternal dietary patterns and macronutrients intake have been shown to affect the development of gestational diabetes mellitus (GDM), but the findings are inconsistent. We aimed to identify maternal dietary patterns and examine their associations with GDM risk, and to evaluate the contributions of macronutrients intake to these associations. We included 2755 Chinese pregnant women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed using a validated semi-quantitative FFQ 2 weeks before the diagnosis of GDM. GDM (n 248) was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24–28 weeks gestation. We derived five different dietary patterns from a principal component analysis. The results showed that high fish–meat–eggs scores, which were positively related to protein intake and inversely related to carbohydrate intake, were associated with a higher risk of GDM (adjusted OR for quartile 4 v. quartile 1: 1·83; 95 % CI 1·21, 2·79; Ptrend=0·007) and higher plasma glucose levels. In contrast, high rice–wheat–fruits scores, which were positively related to carbohydrate intake and inversely related to protein intake, were associated with lower risk of GDM (adjusted OR for quartile 3 v. quartile 1: 0·54; 95 % CI 0·36, 0·83; Ptrend=0·010) and lower plasma glucose levels. In addition, dietary protein and carbohydrate intake significantly contributed to the associations between dietary patterns and GDM risk or glucose levels. These findings suggest that a dietary pattern characterised by high protein and low carbohydrate intake in pregnancy was associated with a higher risk of GDM, which may provide important clues for dietary guidance during pregnancy to prevent GDM.
The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.
Objective
The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.
Methods
Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.
Results
There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (β = 0.31, t = 2.41, p = 0.025).
Conclusions
Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.
Measurement of mean population Na and K intakes typically uses laboratory-based assays, which can add significant logistical burden and costs. A valid field-based measurement method would be a significant advance. In the current study, we used 24 h urine samples to compare estimates of Na, K and Na:K ratio based upon assays done using the field-based Horiba twin meter v. laboratory-based methods.
Design
The performance of the Horiba twin meter was determined by comparing field-based estimates of mean Na and K against those obtained using laboratory-based methods. The reported 95 % limits of agreement of Bland–Altman plots were calculated based on a regression approach for non-uniform differences.
Setting
The 24 h urine samples were collected as part of an ongoing study being done in rural China.
Subjects
One hundred and sixty-six complete 24 h urine samples were qualified for estimating 24 h urinary Na and K excretion.
Results
Mean Na and K excretion were estimated as 170·4 and 37·4 mmol/d, respectively, using the meter-based assays; and 193·4 and 43·8 mmol/d, respectively, using the laboratory-based assays. There was excellent relative reliability (intraclass correlation coefficient) for both Na (0·986) and K (0·986). Bland–Altman plots showed moderate-to-good agreement between the two methods.
Conclusions
Na and K intake estimations were moderately underestimated using assays based upon the Horiba twin meter. Compared with standard laboratory-based methods, the portable device was more practical and convenient.
Iron-deficiency anemia is a public health concern that frequently occurs in pregnant mammals and neonatal offspring. Ferrous N-carbamylglycinate chelate (Fe-CGly) is a newly designed iron fortifier with proven effects in iron-deficient rats and weanling piglets. However, the effects of this new compound on pregnant mammals are unknown. Therefore, this experiment was conducted to evaluate the effects of Fe-CGly on sow reproductive performance and iron status of both sows and neonatal piglets. A total of 40 large-white sows after second parity were randomly assigned to two groups (n=20). They were receiving a diet including 80 mg Fe/kg as FeSO4 or Fe-CGly, respectively, from day 85 of gestation to parturition. The serum (day 110 of pregnancy) and placentas of sows were sampled. Litter size, mean weight of live born piglets, birth (live) litter weight, number of live born piglets, and the number of still-born piglets, mummies, and weak-born piglets were recorded. Once delivered, eight litters were randomly selected from the 20 litters per treatment, and one new-born male piglet (1.503±0.142 kg) from each selected litter was slaughtered within 3 h after birth from the selected litters, without colostrum ingestion. The serum, longissimus muscle, liver and kidneys of the piglets were collected. The iron status of the serum samples and the messenger RNA level of iron-related genes in the placenta, liver and kidney were analyzed. The results showed that litter weight of live born piglets was higher (P=0.030) in the Fe-CGly group (19.86 kg) than in the FeSO4 group (17.34 kg). Fe-CGly significantly increased placental iron concentration (P<0.05) of sows. It also significantly increased iron saturation and reduced the total iron-binding capacity of piglets (P<0.05) at birth. However, the results revealed that supplementation of Fe-CGly in sows reduced liver and kidney iron concentration of neonatal piglets (P<0.05), indicating decreased iron storage. In addition, the concentration of iron in the colostrum was not significantly changed. Therefore, the present results suggested that replacement of maternal FeSO4 supplement with Fe-CGly in the late-gestating period for sows could improve litter birth weight, probably via enhanced iron transportation in the placenta.
135Cs with a half-life of T1/2=2.3×106 yr is an important nuclide in studies of the dispersal of nuclear material in the environment. Preliminary measurements using 133Cs as a proxy for the long-lived 135Cs, with accelerator mass spectrometry (AMS) have been developed at the China Institute of Atomic Energy (CIAE). In order to improve the sensitivity of 135Cs AMS measurement, a new conducting material, Fe powder, was used in the experiment. According to the present results, the background level that can be obtained with blanks was 135Ba/Cs~1.83×10–10 with the CIAE-AMS system. These measurements showed that the Fe was an inferior conducting medium because the interference of 135Ba in Fe powder is 10 times higher than that in Ag powder.