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Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.
The Arsenic (+3 oxidation state) methyltransferase (AS3MT) gene has been identified as a top risk gene for schizophrenia in several large-scale genome-wide association studies. A variable number tandem repeat (VNTR) of this gene is the most significant expression quantitative trait locus, but its role in brain activity in vivo is still unknown.
We first performed a functional magnetic resonance imaging (fMRI) scan of 101 healthy subjects during a memory span task, trained all subjects on an adaptive memory span task for 1 month, and finally performed another fMRI scan after the training. After excluding subjects with excessive head movements for one or more scanning sessions, data from 93 subjects were included in the final analyses.
The VNTR was significantly associated with both baseline brain activation and training-induced changes in multiple regions including the prefrontal cortex and the anterior and posterior cingulate cortex. Additionally, it was associated with baseline brain activation in the striatum and the parietal cortex. All these results were corrected based on the family-wise error rate method across the whole brain at the peak level.
This study sheds light on the role of AS3MT gene variants in neural plasticity related to memory span training.
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.
Disturbances in lipid metabolism are at the core of several health issues facing modern society, including fatty liver and obesity. The sterol regulatory element-binding protein 1 (SREBP-1) is one important transcription factor regulating lipid metabolism, but the relevant mechanism still remains unknown. The present study determined the transcriptional regulation of SREBP-1 and its target genes (including acetyl-CoA carboxylase α (accα), fatty acid synthase (fas) and stearoyl-CoA desaturase 1 (scd1)) in a freshwater teleost, grass carp Ctenopharyngodon idella. We cloned and characterised the 1988 bp, 2043 bp, 1632 bp and 1889 bp sequences of srebp-1, accα, scd1 and fas promoters, respectively. A cluster of putative binding sites of transcription factors, such as specific protein, yin yang 1, nuclear factor Y, sterol response elements (SRE) and enhancer box (E-box) element, were predicted on their promoter regions. Overexpression of nSREBP-1 reduced srebp-1 promoter activity, increased scd1 and fas promoter activity but did not influence accα promoter activity. The site-mutation and electrophoretic mobility shift assay analysis indicated that srebp-1, fas and scd1 promoters, but not accα promoter, possessed SRE. In Ctenopharyngodon idella kidney (CIK) cells of grass carp, nSREBP-1 overexpression significantly reduced srebp-1 mRNA expression and up-regulated miR-29 mRNA expression. The 3′UTR of srebp-1 possessed the potential miR-29 binding site and miR-29 up-regulated the luciferase activity of srebp-1 3′UTR and srebp-1 mRNA expression, implying a self-activating loop of SREBP-1 and miR-29 in grass carp. Based on the above-mentioned results, we found two novel transcriptional mechanisms for SREBP-1 in grass carp: (1) the auto-regulation sited on the SREBP-1 promoter regions was suppressive and (2) there was a self-activating loop of SREBP-1 and miR-29.
To compare and validate neurocognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP) for the China Health and Retirement Longitudinal Study (CHARLS), and to identify appropriate tests to be administered in future waves of CHARLS.
We recruited 825 individuals from the CHARLS sample and 766 subjects from hospitals in six provinces and cities in China. All participants were administered the HCAP-neurocognitive tests, and their informants were interviewed regarding the respondents’ functional status. Trained clinicians administered the Clinical Dementia Rating scale (CDR) to assess the respondents’ cognitive status independently.
The testing protocol took an average of 58 minutes to complete. Refusal rates for tests of general cognition, episodic memory, and language were less than 10%. All neurocognitive test scores significantly correlated with the CDR global score (correlation coefficients ranged from 0.139 to 0.641). The Mini-Mental State Examination (MMSE), the Health and Retirement Study (HRS) - telephone interview for cognitive status (TICS), community screening instrument for dementia (CSI-D) for respondent, episodic memory and language tests each accounted for more than 20% of the variance in global CDR score (p < 0.001) in bivariate tests. In the CHARLS subsample, age and education were associated with neuropsychological performance across most cognitive domains, and with functional status.
A brief set of the CHARLS-HCAP neurocognitive tests are feasible and valid to be used in the CHARLS sample and hospital samples. It could be applied in the future waves of the CHARLS study, and it allows estimating the prevalence of dementia in China through the population-based CHARLS.
Predicting mental workload of pilots can provide cockpit designers with useful information to reduce the possibility of pilot error and cost of training, improve the safety and performance of systems, and increase operator satisfaction. We present a theoretical model of mental workload, using information theory, based on review investigations of how effectively task complexity, visual performance, and pilot experience predict mental workload. The validity of the model was confirmed based on data collected from pilot taxiing experiments. Experiments were performed on taxiing tasks in four different scenarios. Results showed that predicted values from the proposed mental workload model were highly correlated to actual mental workload ratings from the experiments. The findings indicate that the proposed mental workload model appears to be effective in the prediction of pilots’ mental workload over time.
The timing of the Holocene summer monsoon maximum (HSMM) in northeastern China has been much debated and more quantitative precipitation records are needed to resolve the issue. In the present study, Holocene precipitation and temperature changes were quantitatively reconstructed from a pollen record from the sediments of Tianchi Crater Lake in northeastern China using a plant functional type-modern analogue technique (PFT-MAT). The reconstructed precipitation record indicates a gradual increase during the early to mid-Holocene and a HSMM at ~5500–3100 cal yr BP, while the temperature record exhibits a divergent pattern with a marked rise in the early Holocene and a decline thereafter. The trend of reconstructed precipitation is consistent with that from other pollen records in northeastern China, confirming the relatively late occurrence of the HSMM in the region. However, differences in the onset of the HSMM within northeastern China are also evident. No single factor appears to be responsible for the late occurrence of the HSMM in northeastern China, pointing to a potentially complex forcing mechanism of regional rainfall in the East Asian monsoon region. We suggest that further studies are needed to understand the spatiotemporal pattern of the HSMM in the region.
Previous studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.
To detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.
The analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.
Patients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.
The pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.
Major depressive disorder (MDD) is a leading cause of disability worldwide and influenced by both environmental and genetic factors. Genetic studies of MDD have focused on common variants and have been constrained by the heterogeneity of clinical symptoms.
We sequenced the exome of 77 cases and 245 controls of Han Chinese ancestry and scanned their brain. Burden tests of rare variants were performed first to explore the association between genes/pathways and MDD. Secondly, parallel Independent Component Analysis was conducted to investigate genetic underpinnings of gray matter volume (GMV) changes of MDD.
Two genes (CSMD1, p = 5.32×10−6; CNTNAP5, p = 1.32×10−6) and one pathway (Neuroactive Ligand Receptor Interactive, p = 1.29×10−5) achieved significance in burden test. In addition, we identified one pair of imaging-genetic components of significant correlation (r = 0.38, p = 9.92×10−6). The imaging component reflected decreased GMV in cases and correlated with intelligence quotient (IQ). IQ mediated the effects of GMV on MDD. The genetic component enriched in two gene sets, namely Singling by G-protein coupled receptors [false discovery rate (FDR) q = 3.23×10−4) and Alzheimer Disease Up (FDR q = 6.12×10−4).
Both rare variants analysis and imaging–genetic analysis found evidence corresponding with the neuroinflammation and synaptic plasticity hypotheses of MDD. The mediation of IQ indicates that genetic component may act on MDD through GMV alteration and cognitive impairment.
Kaolinite can be used for many applications, including the underground storage of gases. Density functional theory was employed to investigate the adsorption of hydrogen molecules on the kaolinite (001) surface. The coverage dependence of the adsorption sites and energetics was studied systematically for a wide range of coverage, Θ (from 1/16 to 1 monolayer). The three-fold hollow site is the most stable, followed by the bridge, top-z and top sites. The adsorption energy of H2 decreased with increasing coverage, thus indicating the lower stability of surface adsorption due to the repulsion of neighbouring H2 molecules. The coverage has obvious effects on hydrogen adsorption. Other properties of the H2/kaolinite (001) system, including the lattice relaxation and changes of electronic density of states, were also studied and are discussed in detail.
Advanced alloys with both high strength and ductility are highly desirable for a wide range of engineering applications. Conventional alloy design strategies based on the single-principle element are approaching their limits in further optimization of their performances. Precipitation-hardened high-entropy alloys (HEAs), especially those strengthened by coherent L12-nanoparticles, have received considerable interest in recent years, enabling a new space for the development of advanced structural materials with superior mechanical properties. In this review, we highlight recent important advances of the newly developed L12-strengthened HEAs, including the aspects of computation-aided alloy design, unique properties, atomic-level characterization, phase evolution, and stability. In particular, we focus our attention on elucidating fundamental scientific issues involving the alloying effects, precipitation behaviors, mechanical performances, and the corresponding deformation mechanisms, all of which provide a comprehensive metallurgical understanding and guidance for the design of this new class of HEAs. Finally, future research directions and prospects are also critically assessed.
Records of absenteeism from primary schools are valuable data for infectious diseases surveillance. However, the analysis of the absenteeism is complicated by the data features of clustering at zero, non-independence and overdispersion. This study aimed to generate an appropriate model to handle the absenteeism data collected in a European Commission granted project for infectious disease surveillance in rural China and to evaluate the validity and timeliness of the resulting model for early warnings of infectious disease outbreak. Four steps were taken: (1) building a ‘well-fitting’ model by the zero-inflated Poisson model with random effects (ZIP-RE) using the absenteeism data from the first implementation year; (2) applying the resulting model to predict the ‘expected’ number of absenteeism events in the second implementation year; (3) computing the differences between the observations and the expected values (O–E values) to generate an alternative series of data; (4) evaluating the early warning validity and timeliness of the observational data and model-based O–E values via the EARS-3C algorithms with regard to the detection of real cluster events. The results indicate that ZIP-RE and its corresponding O–E values could improve the detection of aberrations, reduce the false-positive signals and are applicable to the zero-inflated data.
In recent years, hand, foot, and mouth disease (HFMD) has been increasingly recognized as a critical challenge to disease control and prevention in China. Previous studies have found that meteorological factors such as mean temperature and relative humidity were associated with HFMD. However, little is known about whether the diurnal temperature range (DTR) has any impact on HFMD. This study aimed to quantify the impact of DTR on childhood HFMD in 18 cities in Sichuan Province. A distributed lag non-linear model was adopted to explore the temporal lagged association of daily temperature with age-, gender- and pathogen-specific HFMD. A total of 290 123 HFMD cases aged 0–14 years were reported in the 18 cities in Sichuan Province. The DTR–HFMD relationships were non-linear in all subgroups. Children aged 6–14 years and male children were more vulnerable to the temperature changes. Large DTR had the higher risk estimates of HFMD incidence in cases of EV71 infection, while small DTR had the higher risk estimates of HFMD incidence in cases of CV-A16 infection. Our study suggested that DTR played an important role in the transmission of HFMD with non-linear and delayed effects.
The icing wind tunnel can simulate the air flow at a high altitude; such an air flow contains supercooled droplets moving at certain velocities. An integrated experiment method was proposed, and it included the icing test and shear stress measurements in the simulated environment of the icing wind tunnel. The error caused by the change in experimental environments was completely eliminated with this novel method. Thus, there was no discrepancy between the real-time and experimental values of shear stress between the ice and substrate. The experiments of icing and shear stress measurements are carried out by varying the following parameters: icing temperature, mean volume diameter (MVD) of droplets, and surface roughness of the substrate. The results indicate that the shear stress between the ice and the substrate increases with the decrease in temperature provided the temperature is relatively high. When the MVD value is 22 μm, the liquid water content is about 1 g/m3 and surface roughness is 2 μm. Under these conditions, the shear stress reaches its maximum value at a temperature of –15°C. The shear stress is also affected by the MVD values of droplets, and the surface roughness of substrate.
The surfacing welding has been widely utilized in the industrial equipment manufacturing and repairs. The wear properties of surfacing alloys have an important effect on the whole performance of repaired components. The solution treatment (T4) and solution treatment followed by aging (T6) effects on the dry sliding wear behavior of surfacing AZ91 magnesium alloys with tungsten inert gas welding were investigated in this work. The results demonstrated that the surfacing alloy without treatment exhibited poor wear resistance, due to the massive intermetallic β-phases (Mg17Al12). These phases were believed to produce stress concentrations in the particle-to-matrix interface and tended to generate cracks during friction. The T4 alloy had more improved wear resistance than the as-received alloy. The T6 treatment improved the wear resistance further, resulting from the high density dispersed fine β-phase precipitation in the α-Mg matrix, which enhanced the alloy strength and hardness and decreased the subsurface metal deformation degree caused by friction.
A stalagmite with high 238U content from Yangkou Cave, China, revealed the evolution of the Asian summer monsoon (ASM) between 49.1 and 59.5 ka, and the δ18O values recorded Dansgaard/Oeschger (D/O) events 13–17. The Yangkou record shows a relatively gradual transition into the D/O 14 and 16 events. The discrepancy between the abrupt and gradual transitions of D/O 14 in the records from northern and southern China, respectively, suggests different responses of the ASM to climate changes in the high northern latitudes. The higher resolution δ18O record and more precise 230Th dating indicate that the timing of D/O 14 and 17 in the Hulu records at 53 and 58 ka should be shifted to 54.3 and 59 ka, respectively. The gradual strengthening of the ASM at the onsets of D/O 16 and 14 in our record is different from the abrupt temperature rise in the northern high latitudes. Some other factors must contribute to this relatively gradual ASM change in southern China, but the actual reason is still unknown.
The deferred correction (DC) method is a classical method for solving ordinary differential equations; one of its key features is to iteratively use lower order numerical methods so that high-order numerical scheme can be obtained. The main advantage of the DC approach is its simplicity and robustness. In this paper, the DC idea will be adopted to solve forward backward stochastic differential equations (FBSDEs) which have practical importance in many applications. Noted that it is difficult to design high-order and relatively “clean” numerical schemes for FBSDEs due to the involvement of randomness and the coupling of the FSDEs and BSDEs. This paper will describe how to use the simplest Euler method in each DC step–leading to simple computational complexity–to achieve high order rate of convergence.
Excavation of the Han Dynasty chambered tomb at Laoguanshan in Chengdu, south-west China, has provided the earliest known evidence of pattern loom technology. Four model looms, along with accompanying artefacts and figurines relating to the weaving process, give insight into the technique of jin silk production. The discovery is hugely significant as it provides the first direct evidence of pattern-weave textile production in ancient China. Jin silk, made using this method, was both valuable and widely distributed, and the design of the machine influenced the invention of later looms and the spread of technology throughout Eurasia and Europe, representing great technological accomplishment for the second century BC.
Palaeoproterozic metasedimentary rocks, also referred to as khondalites, characterized by Al-rich minerals, are extensively exposed in the nucleus of the Yangtze craton, South China block. Samples of garnet–sillimanite gneiss in the khondalite suite were collected from the Kongling complex for Nd isotopic and elemental geochemical study. These rocks are characterized by variable SiO2 contents ranging from 35.71 to 58.07 wt%, and have low CaO (0.45–0.84 wt%) but high Al2O3 (18.56–29.04 wt%), Cr (174–334 ppm) and Ni (42.5–153 ppm) contents. They have high CIW (Chemical Index of Weathering) values (90.4–94.7), indicating intense chemical weathering of the source material. The samples display light rare earth elements (LREE) enrichment with negative Eu anomalies (Eu/Eu*=0.40–0.68), and have flat heavy rare earth elements (HREE) patterns. The high contents of transition elements (e.g. Cr, Ni, Sc, V) and moderately radiogenic Nd isotopic compositions suggest that the paragneisses might be those of first-cycle erosion products of predominantly mafic rocks mixing with small amounts of felsic moderately evolved Archaean crustal source. Geochemical and Nd isotopic compositions reveal that at least some of the protoliths of Kongling khondalite were sourced from local pre-existing mafic igneous rocks in a continental arc tectonic setting. Combined with documented zircon U–Pb geochronological data, we propose that the Palaeoproterozoic high-pressure granulite-facies metamorphism, rapid weathering, erosion and deposition of the khondalites in the interior of the Yangtze craton might be related to a Palaeoproterozoic collisional orogenic event during 2.1–1.9 Ga, consistent with the worldwide contemporary orogeny, implying that the Yangtze craton may have been an important component of the Palaeoprotorozoic Columbia supercontinent.