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Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
Conventional pNIPAAm microgel synthesis utilizes surfactants to suspend pre-gel droplets in the immiscible continuous phase due to the slow polymerization required for synthesizing pNIPAAm in aqueous solvent. To improve the fabrication process and to eliminate the effects of surfactant on microgel quality, a surfactant-free and water-free method was developed. Rapid polymerization of high-quality microgels was achieved in a single-channel microfluidic device to help maintain the integrity of gel particles without the addition of surfactants. The droplet generation mechanism and the effect of flow rate of the two in-going immiscible fluid on the geometry of the produced microgels were studied. The produced microgels have low polydispersity with a dispersity index of 6.4%. The pNIPAAm hydrogels fabricated in the DMSO solvent has smaller pore size and more uniform microstructure compared to that synthesized in water. The fabricated pNIPAAm microgels show a sharp volume phase transition at ∼32 °C and high deswelling/swelling rate.
The evolution of fatigue performance and surface mechanical properties of AISI 304 stainless steel induced by the electropulsing-assisted ultrasonic surface rolling process (EP-USRP) was systematically investigated by integrating instrumented indentation, scanning electron microscopy with electron backscatter diffraction, and transmission electron microscopy. The results indicate that higher hardness, greater strength, finer ultra-refined grains, and higher residual compressive stress are formed within the strengthened layer compared with the original ultrasonic surface rolling process (USRP). EP-USRP with the optimized experimental parameters can produce a higher average rotating bending fatigue strength for AISI 304 stainless steel than USRP. Anomalously and noteworthily, all fatigue specimens treated by EP-USRP showed an incomplete fracture, revealing a higher reservation of safety in practical engineering applications. The further modified structure strengthening and stress strengthening induced by EP-USRP are likely the primary intrinsic reasons for the observed phenomena. Furthermore, the influence mechanism of EP-USRP was discussed scrupulously.
In this work, corrosion-resistant fluoridated Ca–Mg–P composite coatings were prepared on magnesium alloys via a hydrothermal assisted sol–gel process. All these coatings derived from Coating Sols with different F− concentrations are composed of fluoridated hydroxyapatite, magnesium hydroxide, and dittmarite. When F− concentration of Coating Sol is 0.03 M, the coating exhibited uniform and dense surface, and its thickness reached 32 μm, thus possessing a high charge transfer resistance of 312 ± 12.69 kΩ cm2 in simulated body fluid (SBF). Immersion test in SBF showed that this coating could quickly induce the formation of the mineralized layer, implying relatively high bioactivity. After 49 days of immersion, the original composite coating and newly formed mineralized layer reached 60 μm in thickness, providing effective long-term protection for magnesium alloys. These attractive results indicate that this fluoridated Ca–Mg–P composite coating is a promising protective coating on biodegradable magnesium and magnesium alloy implants for orthopaedic applications.
The Solonker and Shalazhashan belts are hotly debated tectonic units of the Central Asian Orogenic Belt (CAOB), because they may either represent a Permian or Triassic suture zone of the CAOB, or a rifting zone overprinted on an Early Palaeozoic orogen. Provenance analysis of the Upper Palaeozoic sandstones in these belts may provide useful constraints on this issue. This study collected six sandstone samples from three study areas: the Mandula area of the Solonker Belt, the Quagan Qulu area of the Shalazhashan Belt but close to the Alxa block, and the Enger Us area of the Shalazhashan Belt, for framework petrography, zircon morphology, U–Pb and Lu–Hf isotopic analyses. Framework petrography reveals that the Mandula and Enger Us area samples contain high proportions of volcanic fragments, whereas the samples from the Quagan Qulu area include not only volcanic fragments but also significant amounts of biotite and muscovite. The detrital zircons of the Mandula area and the Enger Us area yield two main age groups: (i) 260–330 Ma, with dominant εHf(t) values of –5 to +12; and (ii) 420–550 Ma, with dominant εHf(t) values of –9 to +9, suggesting that Early Palaeozoic arc-related magmatic rocks and Late Palaeozoic syn-depositional volcanic rocks are the main source rocks. The detrital zircons of the Quagan Qulu area have one main age group of 420–500 Ma and some grains of 0.9–1.1 Ga, 1.4–1.5 Ga, 1.8–1.9 Ga and ~ 2.5 Ga, which derive from the northern margin of the Alxa block. The lithological and fossil assemblages of the Upper Palaeozoic sandstones suggest shallow-marine to deep-water depositional environments and a northward-deepening transition. Based on the zircon spectra, sedimentary environment analysis and previous studies, we argue that the Solonker Belt and the Shalazhashan Belt of the CAOB are in extensional basins of a fore-arc or rifting setting.
Disclosing the diagnosis of Alzheimer's disease (AD) to a patient is controversial. There is significant stigma associated with a diagnosis of AD or dementia in China, but the attitude of the society toward disclosure of such a diagnosis had not been formally evaluated prior to our study. Therefore, we aimed to evaluate the attitude toward disclosing an AD diagnosis to patients in China with cognitive impairment from their caregivers, and the factors that may affect their attitude.
We designed a 17-item questionnaire and administered this questionnaire to caregivers, who accompanied patients with cognitive impairment or dementia in three major hospitals in Shanghai, China. The caregiver's attitude toward disclosing the diagnosis of AD as evaluated by the questionnaire was compared to that of disclosing the diagnosis of terminal cancer.
A majority (95.7%) of the 175 interviewed participants (mean 14.2 years of education received) wished to know their own diagnosis if they were diagnosed with AD, and 97.6% preferred the doctor to tell their family members if they were diagnosed with AD. If a family member of the participants suffered from AD, 82.9% preferred to have the diagnosis disclosed to the patient. “Cognitive impairment” was the most accepted term by caregivers to disclose AD diagnosis in Chinese.
This study suggests most of the well-educated individuals in a Chinese urban area favored disclosing the diagnosis when they or their family members were diagnosed with AD.
The Myanmar snub-nosed monkey Rhinopithecus strykeri was discovered in 2010 on the western slopes of the Gaoligong Mountains in the Irrawaddy River basin in Myanmar and subsequently in the same river basin in China, in 2011. Based on 2 years of surveying the remote and little disturbed forest of the Gaoligong Mountains National Nature Reserve in China, with outline transect sampling and infrared camera monitoring, a breeding group comprising > 70 individuals was found on the eastern slopes of the Gaoligong Mountains in the Salween River Basin. Given the Critically Endangered status of this primate (a total of < 950 individuals are estimated to remain in the wild), efforts to protect the relatively undisturbed habitat of this newly discovered population and to prevent hunting are essential for the long-term survival of this species.
To examine the acceptability and feasibility of using smartphone technology to assess beverage intake and evaluate whether the feasibility of smartphone use is greater among key sub-populations.
An acceptability and feasibility study of recording the video dietary record, the acceptability of the ecological momentary assessment (EMA), wearing smartphones and whether the videos helped participants recall intake after a cross-over validation study.
Rural and urban area in Shanghai, China.
Healthy adults (n 110) aged 20–40 years old.
Most participants reported that the phone was acceptable in most aspects, including that videos were easy to use (70 %), helped with recalls (77 %), EMA reminders helped them record intake (75 %) and apps were easy to understand (85 %). However, 49 % of the participants reported that they had trouble remembering to take videos of the beverages before consumption or 46 % felt embarrassed taking videos in front of others. Moreover, 72 % reported that the EMA reminders affected their consumption. When assessing overall acceptability of using smartphones, 72 % of the participants were favourable responders. There were no statistically significant differences in overall acceptability for overweight v. normal-weight participants or for rural v. urban residents. However, we did find that the overall acceptability was higher for males (81 %) than females (61 %, P=0·017).
Our study did not find smartphone technology helped with dietary assessments in a Chinese population. However, simpler approaches, such as using photographs instead of videos, may be more feasible for enhancing 24 h dietary recalls.
This study aimed to explore whether the presence of a Y chromosome azoospermia factor (AZF) microdeletion confers any adverse effect on embryonic development and clinical outcomes after intracytoplasmic sperm injection (ICSI) treatment. Fifty-seven patients with AZF microdeletion were included in the present study and 114 oligozoospermia and azoospermia patients without AZF microdeletion were recruited as controls. Both AZF and control groups were further divided into subgroups based upon the methods of semen collection: the AZF-testicular sperm extraction subgroup (AZF-TESE, n = 14), the AZF-ejaculation subgroup (AZF-EJA, n = 43), the control-TESE subgroup (n = 28) and the control-EJA subgroup (n = 86). Clinical data were analyzed in the two groups and four subgroups respectively. A retrospective case–control study was performed. A significantly lower fertilization rate (69.27 versus 75.70%, P = 0.000) and cleavage rate (89.55 versus 94.39%, P = 0.000) was found in AZF group compared with the control group. Furthermore, in AZF-TESE subgroup, the fertilization rate (67.54 versus 74.25%, P = 0.037) and cleavage rate (88.96 versus 94.79%, P = 0.022) were significantly lower than in the control-TESE subgroup; similarly, the fertilization rate (69.85 versus 75.85%, P = 0.004) and cleavage rate (89.36 versus 94.26%, P = 0.002) in AZF-EJA subgroup were significantly lower than in the control-EJA subgroup; however, the fertilization rate and cleavage rate in AZF-TESE (control-TESE) subgroup was similar to that in the AZF-EJA (control-EJA) subgroup. The other clinical outcomes were comparable between four subgroups (P > 0.05). Therefore, sperm from patients with AZF microdeletion, obtained either by ejaculation or TESE, may have lower fertilization and cleavage rates, but seem to have comparable clinical outcomes to those from patients without AZF microdeletion.
Alligatorweed is well known for its potassium (K+)-accumulating capabilities and its strong resistance to undesired growth conditions. The results of this study revealed properties of K+ accumulation and its contribution to drought stress in alligatorweed. In addition, we attempted to characterize the molecular mechanisms of K+ accumulation in this plant. Alligatorweed plants showed a consistent increase in biomass in response to external K+ concentrations, ranging from micromolar levels up to 50 mmol L−1; K+ was also accumulated accordingly in the plants. The stem was the most K+-accumulating organ, accumulating up to 13% of the K+. Moreover, this K+ superaccumulation caused improved resistance to drought stress. The apparent K+ uptake by the roots showed a typical high-affinity property, and the Michaelis constant increased at higher rates of plant K+ in the starting materials. Furthermore, three putative, K+-uptake transporter complementary DNAs (cDNAs) were isolated from alligatorweed (ApKUP1, ApKUP2, and ApKUP3, respectively) using degenerated primers and rapid amplification of cDNA end techniques. The expression of ApKUP1 and ApKUP3 was predominately localized to the leaves, whereas ApKUP2 was expressed throughout the entire plant. The expression of ApKUP1 and ApKUP3 was stimulated in the stems and roots when K+ was depleted from the external medium. Moreover, ApKUP3 expression was enhanced in the stem in response to abscisic acid treatment and drought stress. In conclusion, our findings provide further insight into the mechanisms of K+ accumulation linked to K+ uptake in alligatorweed.
The preference of fertilized (IVF) and somatic cell nuclear transfer (SCNT) presumptive zygotes for different media when cultured in vitro to the blastocyst stage was evaluated in this study. The experiment comprised two zygote production methods (IVF and SCNT) × two culture media (mSOF and G1.5/G2.5) factorial design in which culture droplets that contained approximate 30 presumptive zygotes formed the experimental plots for the assessment of cleavage and blastocyst development. There were 15 to 20 replicates (culture droplets) per treatment combination. Sub-samples 30 to 41 of the blastocysts produced were assessed for cell number and cell apoptosis. A further 10 blastocysts per treatment combination were used for quantitative real-time polymerase chain reaction (RT-PCR) to evaluate the relative abundance of Hsp70 and Bax mRNA. Presumptive zygotes produced by IVF were developmentally more competent than SCNT zygotes in terms of cleavage rate (66.9 vs. 57.0%; P < 0.05) and blastocyst development rates (blastocysts of presumptive zygotes 29.7 vs. 24.8%; blastocysts of cleaved zygotes 44.4 vs. 36.6%; P < 0.05). Over both zygote production systems, however, the results were similar whether culture was in mSOF or in G1.5/G2.5 media for cleavage rate (63.2 vs. 62.4%; P > 0.05) and blastocyst development rate (blastocysts of presumptive zygotes 26.4 vs. 25.7%; P > 0.05; blastocysts of cleaved zygotes 41.8 vs. 41.2%; P > 0.05). There was, however, a significant interaction between the method of zygote production and culture medium for the apoptotic index of blastocysts. The interaction was such that IVF-produced zygotes cultured in mSOF had a lower apoptotic index compared with those cultured in G1.5/G2.5 (4.7 ± 1.2% vs. 9.8 ± 0.9%; P < 0.05) whereas SCNT zygotes had a higher apoptotic index when cultured in mSOF compared with those cultured in G1.5/G2.5 (11.9 ± 1.5% vs. 4.5 ± 1.2%; P < 0.05). Moreover, RT-PCR analysis showed that embryos from IVF-produced zygotes cultured in mSOF had a lower expression level of stress-related and apoptosis genes (Hsp70 and Bax) than those cells cultured in G1.5/G2.5 medium, while SCNT-derived embryos cultured in mSOF had a higher expression level of these genes than those embryos cultured in G1.5/G2.5 medium. The results of this study show that bovine IVF- and SCNT-produced presumptive zygotes have different nutrient requirements for in vitro culture to the blastocyst stage of development. IVF-derived zygotes have a preference for mSOF as the culture medium whereas the G1.5/G2.5 medium is more suitable for the culture of bovine SCNT-derived zygotes.
Energy metabolism, insulin resistance and adiposity have been implicated in breast cancer, but dietary interventions to reduce breast cancer morbidity and mortality have had limited success. MicroRNA (miRNA) are short, non-coding RNA that participate in the control of metabolic processes through the post-transcriptional modification of RNA. We investigated the effect of a low-glycaemic load dietary intervention on miRNA expression, with subsequent bioinformatics pathway analyses to explore metabolic pathways potentially affected by the diet. Total RNA, including miRNA, was isolated from the serum of fourteen otherwise healthy pre-menopausal women with a high breast cancer risk participating in a 12-month dietary intervention designed to lower glycaemic load by at least 15 % from baseline. Genome-wide miRNA expression was conducted using Illumina BeadChips. In the intervention subjects, three differentially expressed miRNA were validated by real-time (RT)-PCR, and in the twenty control participants, four top differentially expressed miRNA were evaluated to confirm a diet effect. In post-intervention v. baseline serum, twenty miRNA were found to be differentially expressed, with twelve up-regulated and eight down-regulated. These differentially expressed miRNA were predicted to be potentially associated with energy balance and cancer pathways based on exploratory enrichment analysis. Quantitative RT-PCR validations in the controls confirmed that the observed miRNA differential expression was dietary intervention induced. Manipulation of dietary glycaemic load has the potential to modify the expression of multiple miRNA predicted to be involved in energy balance and cancer pathways. Further research is necessary to confirm the role of these miRNA in the control of energy metabolism and relationships with cancer-related processes.
Protein tyrosine phosphatase 1B (PTP1B) is implicated in the negative regulation of the insulin signalling pathway by dephosphorylating the insulin receptor (IR) and IR substrates. Ganodermalucidum has traditionally been used for the treatment of diabetes in Chinese medicine; however, its anti-diabetic potency and mechanism in vivo is still unclear. Our previously published study reported a novel proteoglycan PTP1B inhibitor, named Fudan-Yueyang-Ganoderma lucidum (FYGL) from G. lucidum, with a half-maximal inhibitory concentration (IC50) value of 5·12 (sem 0·05) μg/ml, a protein:polyglycan ratio of 17:77 and 78 % glucose in polysaccharide, and dominant amino acid residues of aspartic acid, glycine, glutamic acid, alanine, serine and threonine in protein. FYGL is capable of decreasing plasma glucose in streptozotocin-induced diabetic mice with a high safety of median lethal dose (LD50) of 6 g/kg. In the present study, C57BL/6 db/db diabetic mice were trialed further using FYGL as well as metformin for comparison. Oral treatment with FYGL in db/db diabetic mice for 4 weeks significantly (P < 0·01 or 0·05) decreased the fasting plasma glucose level, serum insulin concentration and the homeostasis model assessment of insulin resistance. FYGL also controlled the biochemistry indices relative to type 2 diabetes-accompanied lipidaemic disorders. Pharmacology research suggests that FYGL decreases the plasma glucose level by the mechanism of inhibiting PTP1B expression and activity, consequently, regulating the tyrosine phosphorylation level of the IR β-subunit and the level of hepatic glycogen, thus resulting in the improvement of insulin sensitivity. Therefore, FYGL is promising as an insulin sensitiser for the therapy of type 2 diabetes and accompanied dyslipidaemia.
The purpose of this study was to prepare intracellular pathogen resistance 1 (Ipr1) transgenic donor cells for somatic cell nuclear transfer (SCNT). Based on our current understanding of Ipr1, a macrophage special expression vector pSP–EGFP–Ipr1was constructed. Bovine fetal fibroblasts were transfected with pSP-EGFP-Ipr1. The green fluorescent protein (GFP)-expressing cells were selected and transferred into enucleated bovine oocytes. Then, the rates of oocyte cleavage and blastocyst formation of transgenic cells and non-transgenic cells were observed, respectively. The results showed that reconstructed embryos derived from transgenic cells could successfully develop into blastocysts, most of which were GFP-positive. This study may provide cloned embryos for the production of anti-tuberculosis transgenic animals.
We report a comprehensive study on the optical properties of GaN- and AlGaN-based lasing structures at high-levels of optical excitation (carrier densities of 1017−1020 cm−3) and identify critical issues necessary for the development of near- and deep-UV light emitting devices. We successfully achieved room temperature stimulated emission (SE) with emission wavelengths ranging from 351 nm to 373 nm in a variety of samples. Through an analysis of the temperature-dependent lasing characteristics, combined with absorption and time-resolved photoluminescence measurements, we estimated the carrier density required to achieve the SE threshold in GaN epilayers. We found that in AlGaN epilayers, the onset of SE (∼1019 cm−3) occurs at carrier densities one order of magnitude higher than in thick GaN epilayers, indicating that an electron-hole plasma is the dominant gain mechanism over the entire temperature range studied (10 K to 300 K). A remarkably low lasing threshold was observed in GaN/AlGaN heterostructures over the temperature range of 10 K to 300 K. Our experimental results indicate that GaN/AlGaN heterostructures could be used to efficiently generate laser emission with wavelengths shorter than 373 nm. The implications of this study on the development of UV laser diodes is discussed.
Gametogenesis is associated with DNA methylation and involves complicated and delicate gene regulation network in which stem cell marker genes exert their functions. Therefore, it is necessary to investigate DNA methylation profiles of those genes in mature gametes that have an effect on embryo development. However, to date, there are limited data available on these genes in mature gametes of bovine. Here we show methylation profiles in 5′ terminal regions of five pluripotency-related genes (Oct4, Sox2, Nanog, Rex1 and Fgf4) in bovine mature gametes, based on the reasoning that the five genes harbour CpG islands in their own 5′ terminal regions, which are frequently the targets of DNA methylation. The results showed that Oct4 and Fgf4 exhibited significant hypermethylation in sperm compared with that in oocytes (p < 0.01), while Sox2 and Nanog displayed relatively the same methylation levels between sperm and oocytes (p > 0.05). Additionally, Rex1 showed a relatively high methylation level in sperm than in oocytes, although no significant differences were found (p > 0.05). In conclusion, bovine mature gametes exhibited two methylation profiles in terms of the five genes, one being non-sex-specific and the other being sex-specific.
In this paper, the ion jet generation from the interaction of an ultraintense laser pulse and a rear-side concave target is investigated analytically using a simple fluid model. We find that the ion expanding surface at the rear-side is distorted due to a strong charge-separation field, and that this distortion becomes dramatic with a singular cusp shown on the central axis at a critical time. The variation of the transverse ion velocity and the relative ion density diverge on the cusp, signaling the emergence of an on-axis ion jet. We have obtained analytical expressions for the critical time and the maximum velocity of the ion jet, and suggested an optimum shape for generating a collimated energetic ion jet. The above theoretical analysis has been verified by particle-in-cell (PIC) numerical simulations.
To identify the disease-causing gene for a large multi-generational Chinese family affected by familial hypertrophic cardiomyopathy (FHCM), genome-wide screening was carried out in a Chinese family with FHCM using micro-satellite markers, and linkage analysis was performed using the MLINK program. The disease locus was mapped to 1q32 in this family. Screening for a mutation in the cardiac troponin T (cTnT) gene was performed by a PCR and sequencing was done with an ABI Prism 3700 sequencer. A novel C→G transition located in the ninth exon of the cTnT gene, leading to a predicted amino acid residue change from Ile to Met at codon 90, was identified in all individuals with hypertrophic cardiomyopathy (HCM). The results presented here strongly suggest that Ile90Met, a novel mutation in the cTnT gene, is causative agent of HCM in this family.
In plants, acid invertases are known to be the key enzymes cleaving sucrose into reducing sugars (RS) (glucose and fructose). To improve the quality of potato (Solanum tuberosum L.) chips, which is largely influenced by RS accumulation in tubers stored at low temperature, a part of acid invertase cDNA with hairpin RNA (hpRNA) structure was transformed into potato cv. N2. Detection of polymerase chain reaction (PCR) amplification and Northern blotting suggested that the RNA interference (RNAi) vector was successfully transformed into cv. N2. The analysis of acid invertase activity in the plantlets and microtubers of RNAi transgenic lines indicated that the expression of the acid invertase was significantly repressed by the activity of RNAi of plantlets by an average 69.8% (with the exception of line Ni-1) with a maximal decrease of 78% (line Ni-4), and the highest decrease of activity in microtubers of 68%. Compared with that of well-inhibited antisense inv transgenic plants, the comparative downregulation of RNAi suggests a distinct alteration of endogenous acid invertase activity and a potential strategy for post-transcriptional gene silencing (PTGS) in modulation of cold-sweetening in potato.