106 research outputs found

    The first comprehensive Milky Way stellar mock catalogue for the Chinese Space Station Telescope Survey Camera

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    The Chinese Space Station Telescope (CSST) is a cutting-edge two-meter astronomical space telescope currently under construction. Its primary Survey Camera (SC) is designed to conduct large-area imaging sky surveys using a sophisticated seven-band photometric system. The resulting data will provide unprecedented data for studying the structure and stellar populations of the Milky Way. To support the CSST development and scientific projects related to its survey data, we generate the first comprehensive Milky Way stellar mock catalogue for the CSST SC photometric system using the TRILEGAL stellar population synthesis tool. The catalogue includes approximately 12.6 billion stars, covering a wide range of stellar parameters, photometry, astrometry, and kinematics, with magnitude reaching down to g=27.5 mag in the AB magnitude system. The catalogue represents our benchmark understanding of the stellar populations in the Milky Way, enabling a direct comparison with the future CSST survey data. Particularly, it sheds light on faint stars that are hidden from current sky surveys. Our crowding limit analysis based on this catalogue provides compelling evidence for the extension of the CSST Optical Survey (OS) to cover low Galactic latitude regions. The strategic extension of the CSST-OS coverage, combined with this comprehensive mock catalogue, will enable transformative science with the CSST

    Epigenetic-Mediated Downregulation of Zinc Finger Protein 671 (ZNF671) Predicts Poor Prognosis in Multiple Solid Tumors

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    Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. However, the methylation status, expression, and prognostic role of ZNF671 in solid tumors remain unclear. The aim of this study was to explore the relationship between ZNF671 and the prognosis of patients with solid tumors. We performed a pan-cancer analysis of the methylation status and mRNA and protein expression of ZNF671 using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. We further evaluated the prognostic value of ZNF671 expression among numerous cancer types using the “Kaplan–Meier plotter” (KM plotter) database. We found that downregulation of ZNF671 is associated with hypermethylation of its promoter. Survival analysis established that the downregulation of ZNF671 predicts poor prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and uterine corpus endometrial carcinoma (UCEC) solid tumors. CCK-8 and Transwell functional assays showed that ZNF671 could inhibit tumor cell proliferation, migration, and invasion. These results indicate that ZNF671 is an excellent predictive factor for BRCA, CESC, HNSC, KIRP, LUAD, PAAD, SARC, and UCEC solid tumors and may play crucial roles in the development and progression of these tumors

    QTL Mapping for Grain Zinc and Iron Concentrations in Bread Wheat

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    Deficiency of micronutrient elements, such as zinc (Zn) and iron (Fe), is called “hidden hunger,” and bio-fortification is the most effective way to overcome the problem. In this study, a high-density Affymetrix 50K single-nucleotide polymorphism (SNP) array was used to map quantitative trait loci (QTL) for grain Zn (GZn) and grain Fe (GFe) concentrations in 254 recombinant inbred lines (RILs) from a cross Jingdong 8/Bainong AK58 in nine environments. There was a wide range of variation in GZn and GFe concentrations among the RILs, with the largest effect contributed by the line × environment interaction, followed by line and environmental effects. The broad sense heritabilities of GZn and GFe were 0.36 ± 0.03 and 0.39 ± 0.03, respectively. Seven QTL for GZn on chromosomes 1DS, 2AS, 3BS, 4DS, 6AS, 6DL, and 7BL accounted for 2.2–25.1% of the phenotypic variances, and four QTL for GFe on chromosomes 3BL, 4DS, 6AS, and 7BL explained 2.3–30.4% of the phenotypic variances. QTL on chromosomes 4DS, 6AS, and 7BL might have pleiotropic effects on both GZn and GFe that were validated on a germplasm panel. Closely linked SNP markers were converted to high-throughput KASP markers, providing valuable tools for selection of improved Zn and Fe bio-fortification in breeding

    Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption

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    Objective: Inspired by the traditionally clinical application of herb pair Zhimu-Huangbo to treat diabetes, a combination of plant ingredients, timosaponin B2 (TB-2) and berberine (BBR), was evaluated for their anti-diabetic efficacy and cooperative mechanisms.Methods: The efficacy and pharmacokinetics of orally administered TB-2 (33.3 mg/kg/day), BBR (66.7 mg/kg/day), and TB-2+BBR (100 mg/kg/day) were evaluated in spontaneously non-obese diabetic Goto-Kakizaki (GK) rats, and metformin (200 mg/kg/day) was used as a positive control. The comparative exposure of the parent drugs, timosaponin A3 (TB-2 metabolite), and M1–M5 (BBR metabolites) was quantified in the portal vein plasma (before hepatic disposition), liver, and systemic plasma (after hepatic disposition) of normal rats on single and combination treatments. Cooperative mechanism of TB-2 and BBR on intestinal absorption and hepatic metabolism was investigated in Caco-2 cells and primary hepatocytes, respectively.Results: After a 6-week experiment, non-fasting and fasting blood glucose levels and oral glucose tolerance test results showed that TB-2+BBR treatments (100 mg/kg/day) displayed significantly anti-diabetic efficacy in GK rats, comparable to that on metformin treatments. However, no significant improvement was observed on TB-2 or BBR treatments alone. Compared to single treatments, combination treatments led to the increased circulating levels of BBR by 107% in GK rats. In normal rats, the hepatic exposure of BBR, timosaponin A3, and M1–M5 was several hundred folds higher than their circulating levels. Co-administration also improved the levels in the plasma and liver by 41–114% for BBR, 141–230% for TB-2, and 12–282% for M1–M5. In vitro, the interaction between TB-2 and BBR was mediated by intestinal absorption, rather than hepatic metabolism.Conclusion: Combining TB-2 and BBR enhanced the anti-diabetic efficacy by increasing the in vivo variety of effective substances, including the parent compounds and active metabolites, and improving the levels of those substances through intestinal absorption. This study is a new attempt to assess the effects of combined plant ingredients on diabetes by scientifically utilizing clinical experience of an herb pair

    Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as RXRα Activator to Inhibit Colon Cancer

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    黄连素是从黄连、黄柏等传统中药中提取的单体化合物,常用于治疗痢疾及其它消化道感染。近年来,黄连素的抗心律失常、调控能量代谢、降血糖血脂和抗癌等多重功效使其成为一个“明星”中药单体化合物。尽管黄连素具有很好的安全性,但其抗癌作用在临床应用上仍具有许多局限性,包括抗癌活性低、溶解度和生物利用度低等。然而,由于黄连素的分子靶点不清楚,以往对黄连素的改造比较盲目和随机,并未取得较好的进展。胡天惠团队与张延东团队紧密合作、优势互补,针对黄连素与RXR的结合模式,运用结构生物学方法和全合成相结合,设计合成了多种黄连素衍生物,并开展了构效关系分析。发现黄连素衍生物B-12在结合并激活RXR、抗肠癌活性、溶解度和生物利用度方面均明显优于黄连素,且保留了黄连素的肿瘤选择性和低毒副作用,具有很好的临床转化前景。该研究也为结构生物学指导黄连素衍生物药物设计提供了理论基础。本论文的通讯作者为医学院占艳艳副教授、张延东教授和胡天惠教授。医学院博士生徐贝贝和化学化工学院博士生江训金为共同第一作者。We reported recently that berberine, a traditional oriental medicine to treat gastroenteritis, binds and activates Retinoid X receptor α (RXRα) to suppress the growth of colon cancer cells. Here, we extended our studies based on the binding mode of berberine with RXRα by design, synthesis and biological evaluation of a focused library of 15 novel berberine analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than berberine, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved berberine’s tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists, or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of berberine-derived RXRα activators as novel effective antineoplastic agents for colon cancer.This work was supported by the National Natural Science Foundation of China (31770860, 21772164, 81572589, 81602560 and 21572187), and the Natural Science Foundation of Fujian Province (2018R1036-2, 2017J06020, 2019R1001-4, and 2019R1001-5). 项目得到了国家自然科学基金委促进海峡两岸科技合作联合基金重点项目、面上项目和福建省自然科学基金的支持

    Efficient synthesis of alkyl levulinates fuel additives using sulfonic acid functionalized polystyrene coated coal fly ash catalyst

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    In this study, sulfonic acid functionalized polystyrene coated coal fly ash catalyst (CFA@PS-SO3H) was designed and prepared by the post-synthesis method, which exhibited excellent catalytic performance for esterification of levulinic acid (LA) to afford alkyl levulinates. Four significant factors, including reaction time, catalyst dosage, alcohol-to-acid molar ratio and reaction temperature were evaluated systematically. Response surface methodology based on Box-Behnken design (BBD) was carried out to determine the optimal parameters. The maximum yield could reach 99.6% under the mild conditions. Furthermore, kinetics of the esterification reaction between levulinic acid and n-butanol were analyzed and the activation energies of the first and second step of esterification reaction were found to 52.18 and 59.81 kJ/mol, respectively. The CFA@PS-SO3H also showed high catalytic activity for the esterification of levulinic acid with other linear alcohols, which made it a low cost, environmentally friendly and promising solid catalyst for the synthesis of alkyl levulinates
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