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The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause–effect relationship remains unclear.
We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia.
We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results.
The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results.
Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.
The razor clam, Sinonovacula constricta, contains high levels of long-chain PUFA (LC-PUFA), which are critical for human health. In addition, S. constricta is the first marine mollusc demonstrated to possess Δ6 fatty acyl desaturase (Fad) and complete LC-PUFA biosynthetic ability, providing a good representative to investigate the molecular mechanism of sterol regulatory element binding proteins (SREBP) in regulating Δ6 Fad for LC-PUFA biosynthesis in marine molluscs. Herein, S. constricta SREBP and Δ6 Fad promoter were cloned and characterised. Subsequently, dual luciferase and electrophoretic mobility shift assays were conducted to explore the SREBP binding elements in the core regulatory region of S. constricta Δ6 Fad promoter. Results showed that S. constricta SREBP had a very conservative basic helix-loop-helix-leucine zipper motif, while S. constricta Δ6 Fad promoter exhibited very poor identity with teleost Fads2 promoters, indicating their differentiation during evolution. A 454 bp region harbouring a core sequence in S. constricta Δ6 Fad promoter was predicted to be essential for the transcriptional activation by SREBP. This was the first report on the regulatory mechanism of LC-PUFA biosynthesis in marine molluscs, which would facilitate optimising the LC-PUFA biosynthetic pathway of bivalves in further studies.
The treatment of refractory schizophrenia has been a clinical challenge for most psychiatrists. The possible mechanism of the refractory schizophrenia included diagnostic errors, medical conditions and brain dysgensis. Here, we described a patient with childhood-onset schizophrenia who had severe psychiatric symptoms such as auditory hallucination and persecutory delusion and so on. We reexamined all his possible medical conditions and found the patient had an abnormal enlarged Cavus Septum Pellucidum (CSP) combined with Cavum Vergae (CV) (maximum length>30 mm). Some reports suggested that abnormal CSP(length>6 mm) has an significant association with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV may lead to schizophrenia and worse prognosis.
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case–control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
Plant cyclophilin (CYP) is related to chloroplast photoprotection, redox and other growth and developmental regulatory processes and responds to stress and improves tolerance to saline–alkali stress. Besides, it exerts peptidyl-prolyl cis/trans isomerase activity to participate in protein synthesis and folding. In this study, Northern blot was used to analyse the CsCYP1A gene (a CYP gene isolated from a Chlorella species) (accession number: KY207381) of tolerant Chlorella vulgaris in soda saline–alkali soil. The result showed that the expression of the CsCYP1A gene was induced by NaHCO3, NaCl and sorbitol. Additionally, Agrobacterium tumefaciens was used to infect the callus of rice (Oryza sativa var. Longjing11) for genetic transformation. Molecular detection confirmed that transgenic seedlings overexpressing CsCYP1A were obtained by hygromycin selection. Treatment with NaCl and NaHCO3 at the five-leaf stage was performed in the seedlings, and the results showed that there were significant differences between the CsCYP1A overexpressed rice lines and non-transgenic (NT) Longjing11 in terms of plant height, fresh weight, chlorophyll content, malondialdehyde content and ascorbate peroxidase activity. The CsCYP1A overexpression rice lines had higher tolerance to NaCl and NaHCO3 than NT. The current findings indicate that CsCYP1A can enhance the tolerance of rice to saline–alkali stress possibly through its involvement in reactive oxygen scavenging pathways.
Taurine (TAU) plays important roles in the metabolism of bile acids, cholesterol and lipids. However, little relevant information has been available in fish where TAU has been identified as a conditionally essential nutrient. The present study aimed to investigate the effects of dietary TAU on the metabolism of bile acids, cholesterol and lipids in tiger puffer, which is both an important aquaculture species and a good research model, having a unique lipid storage pattern. An 8-week feeding trial was conducted in a flow-through seawater system. Three experimental diets differed only in TAU level, that is, 1·7, 8·2 and 14·0 mg/kg. TAU supplementation increased the total bile acid content in liver but decreased the content in serum. TAU supplementation also increased the contents of total cholesterol and HDL-cholesterol in both liver and serum. The hepatic bile acid profile mainly includes taurocholic acid (94·48 %), taurochenodeoxycholic acid (4·17 %) and taurodeoxycholic acid (1·35 %), and the contents of all these conjugated bile acids were increased by dietary TAU. The hepatic lipidomics analysis showed that TAU tended to decrease the abundance of individual phospholipids and increase those of some individual TAG and ceramides. The hepatic mRNA expression study showed that TAU stimulated the biosynthesis of both bile acids and cholesterol, possibly via regulation of farnesoid X receptor and HDL metabolism. TAU also stimulated the hepatic expression of lipogenic genes. In conclusion, dietary TAU stimulated the hepatic biosynthesis of both bile acids and cholesterol and tended to regulate lipid metabolism in multiple ways.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
In this paper, finite amplitude steady-state wave groups with multiple nearly resonant interactions in deep water are investigated theoretically. The nonlinear water wave equations are solved by the homotopy analysis method (HAM), which imposes no constraint on either the number or the amplitude of the wave components, to resolve the small-divisor problems caused by near resonances. A new kind of auxiliary linear operator in the framework of the HAM is proposed to transform the small divisors associated with the non-trivial nearly resonant components to singularities associated with the exactly resonant ones. Primary components, exactly resonant components together with nearly resonant components are considered as the initial non-trivial components, since all of them are homogeneous solutions to the auxiliary linear operator. For wave groups with weak nonlinearity, the energy transfer between nearby nearly resonant components is remarkable. As the nonlinearity increases, the number of steady-state wave groups increases as more components join the near resonance. This indicates that the probability of existence of steady-state resonant waves increases with the nonlinearity of wave groups. The frequency band broadens and spectral asymmetry becomes more and more pronounced. The amplitude of each component may either increase or decrease with the nonlinearity of wave groups, while the amplitude of the whole wave group increases continuously and finite amplitude wave groups are obtained. This work shows the wide existence of steady-state waves when multiple nearly resonant interactions are considered.
Population decline among Asian horseshoe crabs in Asia is increasingly reported, but knowledge of their population and ecological status in China is limited. We conducted community interviews in 30 fishing villages around Beibu Gulf in Guangxi, China, to collect distribution information about the potential spawning/nursery grounds of Tachypleus tridentatus and Carcinoscorpius rotundicauda, and any imminent threats to their populations. Based on the results from 400 respondents we identified 45 potential spawning/nursery grounds distributed widely along the shores of Beibu Gulf. We visited 10 of these sites and verified the presence of juvenile horseshoe crabs by field surveys. Nearly all respondents reported an overall depletion in horseshoe crab populations from these 45 sites, which they attributed mainly to unsustainable fishing practices. Respondents who reported having seen horseshoe crab mating pairs on shores were mostly older people, which may suggest a considerable reduction in horseshoe crabs coming to the shores to spawn in recent years. The mean daily harvest of adult T. tridentatus offshore, as indicated by fishers, has declined from c. 50–1,000 in the 1990s to 0–30 individuals during 2011–2016. Our Wisdom of Crowds approach, supported by confirmatory field surveys, is a cost-effective method for assessing the population status of horseshoe crabs, and the level of threat they face. Similar approaches with other species are likely to be particularly valuable in the Asia–Pacific region, where well-structured population monitoring is largely unaffordable.
To evaluate the effects of different anthropogenic activities on zooplankton and the pelagic ecosystem, we conducted seasonal cruises in 2010 to assess spatial heterogeneity among the mesozooplankton communities of Xiangshan Bay, a subtropical semi-enclosed bay in China. The evaluation included five different areas: a kelp farm, an oyster farm, a fish farm, the thermal discharge area of a power plant, and an artificial reef, and we aimed to identify whether anthropogenic activities dominated spatial variation in the mesozooplankton communities. The results demonstrated clear spatial heterogeneity among the mesozooplankton communities of the studied areas, dominantly driven by natural hydrographic properties, except in the area near the thermal discharge outlet of the power station. In the outlet area, thermal shock caused by the discharge influenced the mesozooplankton community by decreasing abundance and biomass throughout the four seasons, even causing a shift in the dominant species near the outlet during summer from Acartia pacifica to eurythermal and warm water taxa. Unique features of the mesozooplankton community in the oyster farm may be due to the combined effects of oyster culture and the natural environment in the branch harbour. However, kelp and fish culture, and the construction of an artificial reef did not exert any obvious influence on the mesozooplankton communities up to 2010, probably because of the small scale of the aquaculture and a time lag in the rehabilitation effects of the artificial reef. Thus, our results suggested that the dominant factors influencing spatial variations of mesozooplankton communities in Xiangshan Bay were still the natural hydrographic properties, but the thermal discharge was an anthropogenic activity that changed the pelagic ecosystem, and should be supervised.
A total of 1145 samples were collected from chicken breeder farms, hatcheries, broiler farms, a slaughterhouse and retail refrigerated chicken stores in an integrated broiler supply chain in Guangdong Province, China, in 2013. One-hundred and two Salmonella enterica strains were isolated and subjected to serotyping, antimicrobial susceptibility testing, virulence profile determination and molecular subtyping by pulsed field gel electrophoresis (PFGE). The contamination rates in samples from breeder farms, hatcheries, broiler farms, the slaughterhouse and retail stores were 1·46%, 4·31%, 7·00%, 62·86% and 54·67%, respectively. The isolated strains of S. enterica belonged to 10 serotypes; most of them were S. Weltevreden (46·08%, 47/102) and S. Agona (18·63%, 19/102). Isolates were frequently resistant to streptomycin (38·2%), tetracycline (36·3%), sulfisoxazole (35·3%) and gentamicin (34·3%); 31·4% of isolates were multidrug resistant. The isolates were screened for 10 virulence factors. The Salmonella pathogenicity island genes avrA, ssaQ, mgtC, siiD, and sopB and the fimbrial gene bcfC were present in 100% of the strains. PFGE genotyping of the 102 S. enterica isolates yielded 24 PFGE types at an 85% similarity threshold. The PFGE patterns show that the genotypes of S. enterica in the production chain are very diverse, but some strains have 100% similarity in different parts of the production chain, which indicates that some S. enterica persist throughout the broiler supply chain.
The steady-state nearly resonant water waves with time-independent spectrum in deep water are obtained from the full wave equations for inviscid, incompressible gravity waves in the absence of surface tension by means of a analytic approximation approach based on the homotopy analysis method (HAM). Our strategy is to mathematically transfer the steady-state nearly resonant wave problem into the steady-state exactly resonant ones. By means of choosing a generalized auxiliary linear operator that is a little different from the linear part of the original wave equations, the small divisor, which is unavoidable for nearly resonant waves in the frame of perturbation methods, is avoided, or moved far away from low wave frequency to rather high wave frequency with physically negligible wave energy. It is found that the steady-state nearly resonant waves have nothing fundamentally different from the steady-state exactly resonant ones, from physical and numerical viewpoints. In addition, the validity of this HAM-based analytic approximation approach for the full wave equations in deep water is numerically verified by means of the Zakharov’s equation. A thought experiment is discussed, which suggests that the essence of the so-called ‘wave resonance’ should be reconsidered carefully from both of physical and mathematical viewpoints.
This paper describes an experimental investigation of steady-state resonant waves. Several co-propagating short-crested wave trains are generated in a basin at the State Key Laboratory of Ocean Engineering (SKLOE) in Shanghai, and the wavefields are measured and analysed both along and normal to the direction of propagation. These steady-state resonant waves are first calculated theoretically under the exact resonance criterion with sufficiently high nonlinearity, and then are generated in the basin by means of the main wave components that contain at least 95 % of the wave energy. The steady-state wave spectra are quantitatively observed within the inherent system error of the basin and identified by means of a contrasting experiment. Both symmetrical and anti-symmetrical steady-state resonant waves are observed and the experimental and theoretical results show excellent agreement. These results offer the first experimental evidence of the existence of steady-state resonant waves with multiple solutions.
Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (P<0.05); TLR4 mRNA was elevated, but IL-2 was reduced in peripheral blood mononuclear cells (PBMC, P<0.05). The white blood cell count and the percentage of granulocytes (eosinophilic+basophilic) decreased significantly in heat-stressed pigs (P<0.05). In the in vitro model (PBMC heat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (P<0.05). We concluded that a consecutive heat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.
The steady-state fully resonant wave system, consisting of two progressive primary waves in finite water depth and all components due to nonlinear interaction, is investigated in detail by means of analytically solving the fully nonlinear wave equations as a nonlinear boundary-value problem. It is found that multiple steady-state fully resonant waves exist in some cases which have no exchange of wave energy at all, so that the energy spectrum is time-independent. Further, the steady-state resonant wave component may contain only a small proportion of the wave energy. However, even in these cases, there usually exist time-dependent periodic exchanges of wave energy around the time-independent energy spectrum corresponding to such a steady-state fully resonant wave, since it is hard to be exactly in such a balanced state in practice. This view serves to deepen and enrich our understanding of the resonance of gravity waves.
Let f be a transcendental meromorphic function on the complex plane ℂ, let a be a non-zero finite complex number and let n and k be two positive integers. In this paper, we prove that if n≥k+1, then assumes each value b∈ℂ infinitely often. Also, the related normal criterion for families of meromorphic functions is given. Our results generalize the related results of Fang and Zalcman.
The statistical analysis of heating effect and the cross-correlation analysis of both electron temperature and loop voltage have been done during electron cyclotron resonance heating (ECRH). The behavior of runaway electrons in the flat-top phase during ECRH are analyzed using experimental data. It is shown that the runaway population is indeed suppressed or even quenched when the toroidal electric field ET is reduced below the threshold electric field Eth by high-power and long-duration ECRH. The physical mechanism of runaway suppression is explored by the resonant interaction between the electron cyclotron waves and the energetic runaway electrons.
The available data provide inconsistent results on the efficacy of small-dose remifentanil attenuating the cardiovascular response to intubation in children. Therefore, this randomized double-blind study was designed to assess the ability of different small doses of remifentanil on the cardiovascular intubation response in children, with the aim of determining the optimal dose of remifentanil for this purpose.
One hundred and twenty-four children aged 3–9 yr were randomized to one of four groups to receive the following in a double-blind manner: normal saline (Group 1), remifentanil 0.75 μg kg−1 (Group 2), remifentanil 1 μg kg−1 (Group 3) and remifentanil 1.25 μg kg−1 (Group 4). Non-invasive blood pressure and heart rate were recorded before anaesthesia induction (baseline value), immediately before intubation (postinduction values), at intubation and at 1 min intervals for 5 min after intubation.
Tracheal intubation caused significant increases in systolic blood pressure and heart rate in Groups 1–3 compared with the baseline values. The maximum percent increases of systolic blood pressure and heart rate were 10% and 26% of the baseline values, respectively, in Group 2; 5% and 14% in Group 3; and 1% and 8% in Group 4 compared with 27% and 37% in Group 1. Except for the Group 3 vs. Group 4 comparison, there were significant differences among the four groups in the maximum percent increases of systolic blood pressure and heart rate.
When used as part of anaesthesia induction with propofol and vecuronium in children, bolus administration of remifentanil resulted in a dose-related attenuation of the cardiovascular intubation response.
A real-time fluorescent polymerase chain reaction (PCR) assay was established to detect Streptococcus suis serotype 2. Primers and Taqman probe were designed according to cps2I (capsular polysaccharide 2I) gene using bio-software Primer Express2.0 and Oligo6.0. An 81 bp DNA fragment was amplified from S. suis serotype 2 genomic DNA, and the PCR product was cloned into pMD18-T vector and confirmed by DNA sequencing. The real-time fluorescent PCR amplification curve on a Lightcycler® showed that the method is accurate and specific for S. suis serotype 2 amplification, whereas reference bacteria S. suis, Escherichia coli, Salmonella sp., Staphylococcus aureus, Shigella sp., Listeria monocytogenes strains and a blank control were all negative. Tenfold serial dilutions of S. suis serotype 2 were used to measure the sensitivity of real-time fluorescent PCR: ten copies of bacteria could be detected in one PCR reaction and only 30 min were required for a single test. To examine the stability of the real-time fluorescent PCR, the positive control was detected at two different times. The threshold cycle (Ct) values showed no statistical differences (P>0.05). Thus, this method was stable and repeatable. These results indicate that this real-time fluorescent PCR technique could be applied for epidemic supervision in entry–exit inspection and quarantine.