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Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homoeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterisation of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-dehydrocholesterol reductase, which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in the regulation of cholesterol metabolism in fish and may deepen the link between dietary fatty acid and cholesterol biosynthesis.
The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, β-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41–0·89, ORβ-cryptoxanthin = 0·67, 95% CI: 0·49–0·92), chronic bronchitis (ORβ-cryptoxanthin = 0·66, 95% CI: 0·50–0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62–0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42–0·90, HRα-carotene = 0·54, 95% CI: 0·36–0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33–0·71, HRlycopene = 0·66, 95% CI: 0·45–0·96) than those in the lowest tertiles. Higher serum total carotenoids and β-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.
This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.
In recent years, the controlling nutritional status (CONUT) score has increasingly became an effective indicator associated with tumor prognosis. This study was conducted to synthesise data on the prognostic value of CONUT score on patients with upper tract urothelial carcinoma (UTUC) or renal cell carcinoma (RCC) undergoing nephrectomy. We designed and performed a systematic analysis of studies that verified the correlation between preoperative CONUT score and prognosis for UTUC and RCC using PubMed, Web of Science and Embase. The conclusion was clarified by pooled hazard ratios (HR) and 95% confidence intervals (95% CI). Subgroup analysis were further conducted in accordance with different primary tumor. Six studies involving 3529 patients were included in this evidence synthesis, which revealed that the CONUT score had a potential role to predict the survival of UTUC and RCC patients accepting surgery. Pooled analysis showed that the overall survival (OS, HR 2·32, p < 0·0001), cancer-specific survival (CSS, HR 2·68, p < 0·0001) and disease-free survival (DFS, HR 1·62, p < 0·00001) were inferior in the high CONUT score group when compared with low score group. Subgroup analysis revealed that this result was in line with UTUC (OS: HR 1·86, p = 0·02; CSS: HR 2·24, p = 0·01; DFS: HR 1·54, p < 0·00001) and RCC (OS: HR 3·05, p < 0·00001; CSS: HR 3·47, p < 0·00001; DFS: HR 2·21, p = 0·0005) patients respectively. Consequently, the CONUT score is a valuable preoperative index to predict the survival of patients with UTUC or RCC undergoing nephrectomy.
A 1178 J near diffraction limited 527 nm laser is realized in a complete closed-loop adaptive optics (AO) controlled off-axis multi-pass amplification laser system. Generated from a fiber laser and amplified by the pre-amplifier and the main amplifier, a 1053 nm laser beam with the energy of 1900 J is obtained and converted into a 527 nm laser beam by a KDP crystal with 62% conversion efficiency, 1178 J and beam quality of 7.93 times the diffraction limit (DL). By using a complete closed-loop AO configuration, the static and dynamic wavefront distortions of the laser system are measured and compensated. After correction, the diameter of the circle enclosing 80% energy is improved remarkably from 7.93DL to 1.29DL. The focal spot is highly concentrated and the 1178 J, 527 nm near diffraction limited laser is achieved.
In this paper, we report the study of degradation for a kind of ideal mandrel material called poly-α-methylstyrene based on theoretical and experimental methods. First-principles calculations reveal two types of process: depolymerization and hydrogen-transfer-induced chain scission. The energy barrier for the former (0.68–0.82 eV) is smaller than that for most of the latter (1.39–4.23 eV). More importantly, reaction rates suggest that the former is fast whereas the latter is mostly slow, which can result in a difference of 5–31 orders of magnitude at 550 K. Furthermore, a thermogravimetric experiment shows that the activation energy of 2.53 eV for degradation is between those of fast and slow processes, corresponding to the theoretical average value of multiple reaction paths. Thus, a mandrel degradation model combining fast and slow processes is established at the atomic level. Our work provides a direction for research into the key technology of target fabrication in inertial confinement fusion.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
Bragg coherent X-ray diffraction imaging has been used to determine the structure of the initial clusters of α-Fe nano crystals which form upon annealing of an iron-based amorphous alloy or metallic glass. The method is able to identify the shapes and strain of these crystallites without any need for cutting the sample, so can visualize them in three dimensions in their intact state. In this way, the delicate dendritic structures on the exterior of the crystallites can be seen and its density versus radius relationship identifies a fractal dimension of the porous region that is consistent with diffusion-limited aggregation models. The crystal sizes were found to be around 60 nm after annealing at 700 °C growing to about 330 nm after annealing at 750 °C. This article introduces the BCDI method and describes its application to characterize previously recrystallized samples of iron-based amorphous alloys. It paves the way for a possible future in situ nucleation/growth investigation of the relationship between kinetics and nanostructure of metallic glass.
Tenuazonic acid (TeA), a naturally occurring product of Alternaria alternata, a pathogen to croftonweed, was discovered to be a novel natural photosystem II (PSII) inhibitor. However, herbicidal activity of AAC-toxin, a metabolite of this fungus containing TeA as the main active ingredient, has not been evaluated systematically. In this study, we conducted activity-evaluation experiments in the laboratory, greenhouse, and field trials to assess the herbicidal potential of this fungal metabolite. AAC-toxin had high herbicidal activity on all species tested: croftonweed, large crabgrass, barnyardgrass, redroot pigweed, and eclipta. The AAC-toxin caused brown, leaf spot symptoms and leaf necrosis, subsequently killing the seedlings. When AAC-toxin was applied POST at 83 ml ai/ha, more than 95% of large crabgrass, barnyardgrass, and redroot pigweed plants were controlled 2 d after treatment in field trials. It can be concluded that AAC-toxin has broad-spectrum, rapid, and high herbicidal activity similar to that of paraquat and may have the potential to be developed as a microbe-based herbicide.
NRGN is one of the most promising candidate genes for schizophrenia based on function and position. Therefore, this study aimed to examine the genetic association of this polymorphism with schizophrenia in the Zhuang and Han populations of south China.
Subjects and methods
A total of 282 patients (188 Han and 94 Zhuang) and 282 healthy subjects (188 Han and 94 Zhuang) were recruited. Of these, 246 schizophrenia patients underwent an assessment of psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS). A TaqMan genotyping assay method was used to determine the genotypes.
We did not find a significant association of rs12807809 polymorphism with schizophrenia in the total pooled samples, or in the separate ethnic groups. However, in Han schizophrenia patients, quantitative data analyses showed that the CC genotype of the rs12807809 polymorphism was associated with PANSS aggression subscale score and activation subscale score. Furthermore, carriers of the C allele of rs12807809 polymorphism among Han schizophrenia patients had higher scores of general, activation, depression, aggression, and global symptoms than the T allele carriers.
In conclusion rs12807809 polymorphism may not contribute to the risk of schizophrenia but influence the clinical symptoms of schizophrenia in the Han population.
Considerable controversy exists regarding the associations of dietary patterns with the risk of all-cause, CVD and stroke mortality. Therefore, a meta-analysis was conducted to elucidate the potential associations between dietary patterns and the risk of all-cause, CVD and stroke mortality. The PubMed database was searched for prospective cohort studies on the associations between dietary patterns and the risk of all-cause, CVD and stroke mortality published until February 2014. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest v. the lowest category of dietary pattern scores. Stratified analyses were conducted based on sex, geographical region, follow-up duration, and adjustment/non-adjustment for energy intake. A total of thirteen prospective cohort studies involving 338 787 participants were included in the meta-analysis. There was evidence of inverse associations between the prudent/healthy dietary pattern and the risk of all-cause (SRRE = 0·76, 95 % CI 0·68, 0·86) and CVD (SRRE = 0·81, 95 % CI 0·75, 0·87) mortality and an absence of association between this dietary pattern and stroke mortality (SRRE = 0·89, 95 % CI 0·77, 1·02). However, no significant associations were observed between the Western/unhealthy dietary pattern and the risk of all-cause (SRRE = 1·07, 95 % CI 0·96, 1·20), CVD (SRRE = 0·99, 95 % CI 0·91, 1·08) and stroke (SRRE = 0·94, 95 % CI 0·81, 1·10) mortality. In conclusion, the findings provide evidence that greater adherence to a prudent/healthy dietary pattern is associated with a lower risk of all-cause and CVD mortality and not significantly associated with stroke mortality and that the Western/unhealthy dietary pattern is not associated with all-cause, CVD and stroke mortality. Further studies are required to confirm these findings.
The present study aims to evaluate the antiparasitic activity of active components from Costus speciosus against Ichthyophthirius multifiliis. Bioassay-guided fractionation was employed to identify active compounds from C. speciosus yielding 2 bioactive compounds: Gracillin and Zingibernsis newsaponin. In-vitro assays revealed that Gracillin and Zingibernsis newsaponin could be 100% effective against I. multifiliis at concentrations of 0·8 and 4·5 mg L−1, with median effective concentration (EC50) values of 0·53 and 3·2 mg L−1, respectively. All protomonts and encysted tomonts were killed when the concentrations of Gracillin and Zingibernsis newsaponin were 1·0 and 5·0 mg L−1. In-vivo experiments demonstrated that fish treated with Gracillin and Zingibernsis newsaponin at concentrations of 1·0 and 5·0 mg L−1 carried significantly fewer parasites than the control (P<0·05). Mortality of fish did not occur in the treatment group (Zingibernsis newsaponin at 5·0 mg L−1) during the trial, although 100% of untreated fish died. Acute toxicities (LD50) of Gracillin and Zingibernsis newsaponin for grass carp were 1·64 and 20·7 mg L−1, respectively. These results provided evidence that the 2 compounds can be selected as lead compounds for the development of new drugs against I. multifiliis.
Schizophrenia (SZ) is a common severe psychiatric disorder and a complex polygenic inherited disease that has not yet been fully interpreted. Heredity was proven to play an important role in the development of SZ. The association between the NOTCH4 gene rs3131296 polymorphism and SZ was reported to reach significance at the genome-wide level; therefore, it is necessary to replicate this association in other different populations.
To evaluate the association of the NOTCH4 gene rs3131296 polymorphism with the risk for SZ, and to explore whether a significant association could be replicated in different ethnic groups of China, we conducted this case–control study on 282 SZ cases (188 Han and 94 Zhuang) and 282 controls (188 Han and 94 Zhuang) among the Chinese Zhuang and Han populations.
The results showed no statistically significant difference in the genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between SZ patients and healthy controls in either the Zhuang or Han samples (p > 0.05). In addition, no significant difference was found in genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between cases and controls in the combined samples including Zhuang and Han samples.
Our study failed to replicate the significant association between the NOTCH4 gene rs3131296 polymorphism and the risk for SZ.
Based on 187 galaxy clusters identified from the photometric redshifts of galaxies in the Cosmic Evolution Survey (COSMOS) field(Wen & Han 2011), cluster galaxies brighter than MV = -20.5 are classified into four categories according to their best-fitting templates of the spectral energy distributions (SEDs) provided by Ilbert et al. (2009): early-type (including elliptical and lenticular) galaxies (E+S0), spiral galaxies (S), irregular galaxies (Irr), and starbursts (SB). The fractions of these four SED types are presented as the functions of redshift in Figure 1. Fraction of each category varies remarkably with cluster redshift: fractions of normal galaxies (E+S0+S+Irr) tend to decrease with redshift, whilst the starburst proportion tends to increase with redshift. For the normal galaxies, there exists a sequence for the decreasing slopes of morphological fractions. Majority of the galaxies in high-redshift clusters (z > 1.0) are experiencing strong star-formation activities, which leads to a very high proportion of starburst.
The challenges associated with meeting 20nm technology requirements for better Cu CMP process uniformity and lower defectivity have been studied. Required improvements in uniformity were obtained through platen process optimization along with evaluation & selection of specific Cu slurries and pads and their performance reported. The principal factors influencing defect formation, including Cu barrier metallurgy, interconnect pattern density and process queue times were studied. Specific new post CMP clean chemistries were evaluated to assess their capability to suppress defect formation and their performance reported. The trade off between uniformity and defect suppression as a function slurry, pad and post Cu CMP clean chemistry is described.
We have demonstrated and studied polymeric solid-state dye lasers (SSDLs) fabricated by three-dimensional (3D) polystyrene colloidal crystals and tert-butyl roadamine B (t-Bu RhB) doped Poly (methyl methacrylate) (PMMA) films with different film thickness. The sandwich-typed resonator cavities with different active layer thickness display single-mode lasing oscillations in the reflection bandgap of the colloidal crystals. The lasing thresholds could be optimized by changing the thickness of t-Bu RhB doped PMMA films, which is as low as 7.43 W/cm2. Adjusting active layer thickness would provide an opportunity to accelerate the development of fabricating polymeric SSDLs with low threshold.