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HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor

Current Medical Science 2023年第6期43卷 1116-1132页

作者： Yu-feng ZUO bao-hua ZHANG Ming-rui GUO Ben-ben LI bao-cui wang Deng DUAN Yu-xin wang Jing XI Meng HE Tao-lei SUN School of Chemistry Chemical Engineering and Life SciencesWuhan University of TechnologyWuhan430070China The National Clinical Research Center for Mental Disorders&Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital&the Advanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing100069China Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases School of ChemistryChemical Engineering and Life ScienceWuhan University of TechnologyWuhan430070China

Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary *** study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet(HFD)and explored the involvement of endoplasmic reticulum(ER)*** Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine(3 mg/kg/day)and the ER stress inhibitor 4-phenylbutyric acid(4-PBA,1 and 0.5 g/kg/day)for 8 *** in body weight,food intake,and plasma lipids were *** fat accumulation was evaluated using oil red O *** blotting and immunofluorescence assays were employed to examine the expression of ER stress markers,NOD-like receptor pyrin domain-containing protein 3(NLRP3),and proopiomelanocortin(POMC)in the hypothalamus or *** Compared to olanzapine alone,olanzapine+HFD induced greater weight gain,increased hyperlipidemia,and enhanced hepatic fat accumulation(P<0.05).Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects(P<0.05).Further mechanistic investigations revealed that olanzapine alone activated ER stress,upregulated NLRP3 expression in the hypothalamus and liver,and downregulated hypothalamic POMC *** HFD exacerbated these effects by 50%–100%.Moreover,co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress,NLRP3,and POMC expression in the hypothalamus and liver(P<0.05).Conclusion HFD worsened olanzapine-induced weight gain and lipid metabolic disorders,possibly through ER stress-POMC and ER stress-NLRP3 *** stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.

关键词： olanzapine high-fat diet obesity lipid metabolism endoplasmic reticulum stress proopiomelanocortin NOD-like receptor pyrin domain-containing protein 3

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Porcine Interleukin-2 Expression in Insect Cells and Its Enhancement of Pig Immunity to Swine Influenza Virus Inactivated Vaccine

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Agricultural Sciences in China 2010年第8期9卷 1211-1220页

作者： CHEN Hong-ying ZHANG Hong-ying HUANG Yan-quan cui bao-an wang Zhen-ya wang Yan-bin LIU Jin-peng CHAO An-jun College of Animal Husbandry and Veterinary Henan Agricultural University Zhengzhou 450002 P.R.China

Mature porcine interleukin-2 （pIL-2） gene was amplified by PCR from the plasmid pGEM-T-pIL2 and cloned into the baculovirus pFastBacTM Dual vector of the Bac-to-Bac baculovirus expression system under the control of the PH promoter. Recombinant plL-2 （rpIL-2） expressed in Sf9 insect cells was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunofluorescence assay. Western blot analysis confirmed that the rpIL-2 protein had a molecular mass of 20 kDa, which was larger than the molecular mass of the mature protein predicted based on its peptide sequence. The rpIL-2 protein induced in vitro proliferation of ConA-stimulated porcine splenocytes and enhanced in vivo protective immune responses induced by vaccinating the pigs with inactivated oil emulsion vaccine against swine influenza virus. The results showed that the rpIL-2 expressed in Sf9 insect cells has immunoenhancement effects; the finding lays the foundation for the preparation of a specific recombinant IL-2 protein and the development of a novel immune adjuvant of vaccines against various infectious porcine pathogens to increase the immunoprotective efficacy of vaccines.

关键词： porcine interleukin-2 Sf9 insect cells expression inactivated vaccine swine influenza virus

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： wang Han Lin XUE Yan Feng cui bao Qiu LIU Hong SHEN Xin Xin Shandong Provincial Research Center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with *** We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 *** MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for *** variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary *** The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for ***,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of *** contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against *** This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

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Artemordins A-S, Cadinane-Type Sesquiterpenoid Dimers from Artemisia ordosica and Their Antihepatoma Activities

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Chinese Journal of Chemistry 2024年第13期42卷 1493-1508页

作者： Yuan wang Tian-Ze Li Yun-bao Ma Chang-An Geng Yong-cui wang Ji-Jun Chen State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunmingYunnan 650201China University of Chinese Academy of Sciences Beijing 100049China

Nineteen new cadinane-involving sesquiterpenoid dimers,artemordins A-S(1-—19),together with 13 known SDs(20-32)were isolated from Artemisia *** structures and absolute configurations were established by comprehensive spectral analyses,X-ray single crystal diffraction,theoretical ECD,and NMR ***,artemordins A-F(1—6)were the first examples of two cadinane units constructed by unprecedented C-3−C-15′or C-3−C-13′single bond with an oxido-rearranged 6/5/6/6 fused ring system;artemordins G-K(7-11)were biogenetically connected by[4+2]cycloaddition reaction and artemordins G-J(7-10)possessed a novel 5/6/6/6/6/6/5-heptacyclic fused ring *** L-S(12-19)were formed by esterification,which involved three different types of *** assay suggested that the most active compounds,artemordins B and H(2 and 8),exhibited inhibitory activities on three hepatoma cell lines with IC50 values of 26.9 and 25.1μmol/L(HepG2),29.5 and 18.3μmol/L(Huh7),19.7 and 15.7μmol/L(SK-Hep-1).

关键词： Artemisia ordosica Artemordins A-s Cadinane-type sesquiterpenoid dimers Antihepatoma activities Terpenoids Natural products Cytotoxicity

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New steelmaking process based on clean deoxidation technology

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1249-1262页

作者： Zhongliang wang Yanping bao State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

After the converter steelmaking process,a considerable number of ferroalloys are needed to remove dissolved oxygen from the molten steel,but it also forms a lot of oxide inclusions that cannot be completely *** the same time,it increases the carbon emis-sions in the steel production *** years of research,our team have developed a series of clean deoxidation technologies,includ-ing carbon deoxidation,hydrogen deoxidation,and waste plastic deoxidation of molten steel to address the aforementioned *** this study,thermodynamic calculations and laboratory experiments were employed to verify that carbon and hydrogen can reduce the total oxygen content in the molten steel melt to below 5×10^(-6) and 10×10^(-6),*** analysis of the deoxidation mechanisms and ef-fects of polyethylene and polypropylene was also *** addition,the applications of carbon deoxidation technology in different steels with the hot-state experiment and industrial production were discussed *** carbon deoxidation experimental results of different steels were as follows:(1)the oxygen content of bearing steel was effectively controlled at 6.3×10^(-6) and the inclusion number density was lowered by 74.73%compared to aluminum deoxidized bearing steel;(2)the oxygen content in gear steel was reduced to 7.7×10^(-6) and a 54.49%reduction of inclusion number density was achieved with almost no inclusions larger than 5μm from the average level of industry gear steels;(3)a total oxygen content of M2 high-speed steel was as low as 3.7×10^(-6).In industrial production practice,car-bon deoxidation technique was applied in the final deoxidation stage for non-aluminum deoxidized bearing steel,and it yielded excellent results that the oxygen content was reduced to below 8×10^(-6) and the oxide inclusions in the steel mainly consist of silicates,along with small amounts of spinel and calcium aluminate.

关键词： clean deoxidation carbon deoxidation hydrogen deoxidation waste plastics deoxidation

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Development and prospects of molten steel deoxidation in steelmaking process

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 18-32页

作者： Zhongliang wang Yanping bao State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

In the long traditional process of steelmaking,excess oxygen is blown into the converter,and alloying elements are used for *** inevitably results in excessive deoxidation of products remaining within the steel liquid,affecting the cleanliness of the *** the increasing requirements for steel performance,reducing the oxygen content in the steel liquid and ensuring its high cleanliness is *** more than a hundred years of development,the total oxygen content in steel has been reduced from approximately 100×10^(-6)to approximately 10×10^(-6),and it can be controlled below 5×10^(-6)in some steel grades.A relatively stable and mature deoxidation technology has been formed,but further reducing the oxygen content in steel is no longer significant for improving steel *** research team developed a deoxidation technology for bearing steel by optimizing the entire conventional *** technology combines silicon–manganese predeoxidation,ladle furnace diffusion deoxidation,and vacuum final *** successfully conducted industrial experiments and produced interstitial-free steel with natural decarbonization ***-aluminum deoxidation was found to control the oxygen content in bearing steel to between 4×10^(-6) and 8×10^(-6),altering the type of inclusions,eliminating large particle Ds-type inclusions,improving the flowability of the steel liquid,and deriving a higher fatigue *** natural decarbonization predeoxidation of interstitial-free steel reduced aluminum consumption and production costs and significantly improved the quality of cast billets.

关键词： steel deoxidation deoxidizer metallurgical equipment bearing steel IF steel

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Number of Solitons Emerged in the Initial Profile of Shallow Water Using Convolutional Neural Networks

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Journal of Systems Science & Complexity 2024年第2期37卷 463-479页

作者： wang Zhen cui Shikun School of Mathematical Sciences Dalian University of TechnologyDalian 116024China School of Mathematical Sciences Beihang UniversityBeijing 100191China

The soliton resolution conjecture proposes that the initial value problem can evolve into a dispersion part and a soliton ***,the problem of determining the number of solitons that form in a given initial profile remains unsolved,except for a few specific *** this paper,the authors use the deep learning method to predict the number of solitons in a given initial value of the Korteweg-de Vries(KdV)*** leveraging the analytical relationship between Asech^(2)(x)initial values and the number of solitons,the authors train a Convolutional Neural Network(CNN)that can accurately identify the soliton count from spatio-temporal *** trained neural network is capable of predicting the number of solitons with other given initial values without any additional *** extensive calculations,the authors demonstrate the effectiveness and high performance of the proposed method.

关键词： Convolutional neural network deep learning method KdV equation soliton

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Mechanical Behavior and Failure Mechanism of an As-Extruded Mg-11wt%Y Alloy at Elevated Temperature

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Acta Metallurgica Sinica(English Letters) 2024年第6期37卷 969-981页

作者： Lan Zhang Dao-Kui Xu bao-Jie wang cui-Lan Lu Shuo wang Xiang-Bo Xu Dong-Liang wang Xin Lv En-Hou Han School of Materials Science and Engineering University of Science and Technology of ChinaShenyang110016China Key Laboratory of Nuclear Materials and Safety Assessment Institute of Metal ResearchChinese Academy of SciencesShenyang110016China School of Environmental and Chemical Engineering Shenyang Ligong UniversityShenyang110159China Key Lab of Electromagnetic Processing of Materials Ministry of EducationNortheastern UniversityShenyang110819China Institute of Corrosion Science and Technology Guangdong510070China

Through carrying out the high-temperature tensile experiments on an as-extruded Mg-11wt%Y alloy at 350℃,400℃,450℃,500℃and 550℃,the mechanical behavior and fracture mechanisms at elevated temperatures are investigated and *** results show that with the increase of temperature,the yield strength and ultimate tensile strength of the alloy increase at first and then decrease,while that the elongation ratio decreases firstly and then *** the sample being tested at 350℃,the values of yield strength,ultimate tensile strength and the elongation ratio are 188 MPa,266 MPa and 11%,*** 400℃,the yield strength and ultimate tensile strength reach the maximum values of,respectively,198 MPa and 277 MPa,but the elongation ratio is the lowest and its value is only 8%.When the applied temperature is increased to 550℃,the values of yield strength and ultimate tensile strength,respectively,decrease to 140 MPa and 192 MPa and the elongation ratio increases to 38%.Failure analysis demonstrates that the fracture surfaces of different samples are mainly composed of plastic dimples and exhibit the typical characteristic of ductile *** observation to the fracture side surfaces indicates that at the temperatures of 350℃and 400℃,microcracks mainly initiate in the interior of Mg_(24)Y_(5)*** the temperatures are 450℃,500℃and 550℃,the cracks preferentially initiate at the Mg_(24)Y_(5)/α-Mg interfaces.

关键词： Mg-Y alloy High-temperature tensile properties Fracture mechanism Failure analysis

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Lunar In Situ Large-Scale Construction:Quantitative Evaluation of Regolith Solidification Techniques

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Engineering 2024年第8期39卷 204-221页

作者： Charun bao Daobo Zhang Qinyu wang Yifei cui Peng Feng MOE Key Laboratory of Civil Engineering Safety and Durability Department of Civil EngineeringTsinghua UniversityBeijing 100084China State Key Laboratory of Hydroscience and Engineering Tsinghua UniversityBeijing 100084China

Lunar habitat construction is crucial for successful lunar exploration *** to the limitations of transportation conditions,extensive global research has been conducted on lunar in situ material processing techniques in recent *** aim of this paper is to provide a comprehensive review,precise classification,and quantitative evaluation of these approaches,focusing specifically on four main approaches:reaction solidification(RS),sintering/melting(SM),bonding solidification(BS),and confinement formation(CF).Eight key indicators have been identified for the construction of low-cost and highperformance systems to assess the feasibility of these methods:in situ material ratio,curing temperature,curing time,implementation conditions,compressive strength,tensile strength,curing dimensions,and environmental *** scoring thresholds are determined by comparing the construction requirements with the actual *** the evaluated methods,regolith bagging has emerged as a promising option due to its high in situ material ratio,low time requirement,lack of hightemperature requirements,and minimal shortcomings,with only the compressive strength falling below the neutral *** compressive strength still maintains a value of 2–3 *** proposed construction scheme utilizing regolith bags offers numerous advantages,including rapid and large-scale construction,ensured tensile strength,and reduced reliance on equipment and *** this study,guidelines for evaluating regolith solidification techniques are provided,and directions for improvement are *** proposed lunar habitat design based on regolith bags is a practical reference for future research.

关键词： Lunar habitats Lunar in situ construction Regolith bag Solidification and formation In situ materials Evaluation method

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Three Types of Isocoumarins with Unusual Carbon Skeletons from Artemisia dubia var. subdigitata and Their Antihepatoma Activity

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Chinese Journal of Chemistry 2024年第16期42卷 1901-1912页

作者： Ke-Xin Yang Tian-Ze Li Yun-bao Ma Yong-cui wang Feng-Jiao Li Ji-Jun Chen State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunmingYunnan 650201China University of Chinese Academy of Sciences Beijing 100049China

Ten novel isocoumarins,including four pairs of enantiomers,were isolated from Artemisia dubia ***(Asteraceae).Compounds 1,2 and 3a/3b possessed a unique 6/6/6-tricyclic system comprising an unusual 1-(2-methylcyclohexyl)propan-1-one moiety fused with isocoumarin core *** 4a/4b were characterized as an unexpected 2,5-dimethylcyclohexan-1-one scaffold,and compounds 5a/5b and 6a/6b were rare 1,*** structures and absolute configurations were elucidated through spectroscopic data,X-ray crystallography,ECD and NMR calculations with DP4+*** biosynthetic pathways were proposed from the naturally occurring *** pharmacological analysis suggested that the targets of compound 1 were significantly enriched in the cell cycle and Pl3K-Akt signaling *** molecular docking revealed that compound 1 had high binding affinity with CDK2(total score:6.8717).Furthermore,compounds 1 and 2 exhibited inhibitory activity on three human hepatoma cell lines,with inhibitory ratios of 85.1% and 84.5%(HepG2),88.2% and 87.3%(Huh7),and 69.2% and 69.1%(SK-Hep-1)at 200μmol·L^(-1),respectively.

关键词： Artemisia dubia var.subdigitata Isocoumarins Antihepatoma activity Cancer Natural products X-ray diffraction

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