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Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation

Acta Pharmaceutica Sinica B 2022年第4期12卷 1899-1912页

作者： Pengcheng Wang Guangyi Zeng Yu Yan Song-yang Zhang Yongqiang Dong Yangming Zhang Xingzhong Zhang huiying liu Zhipeng Zhang Changtao Jiang Yanli Pang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191 China Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191 China Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijing 100191China General Surgery Department Peking University Third HospitalBeijing 100191China

Atherosclerosis is a chronic multifactorial cardiovascular disease.Western diets have been reported to affect atherosclerosis through regulating adipose function.In high cholesterol diet-fed ApoE^(−/−)mice,adipocyte HIF-1αdeficiency or direct inhibition of HIF-1αby the selective pharmacological HIF-1αinhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation,which lowers cholesterol levels and reduces inflammatory responses,resulting in improved dyslipidemia and atherogenesis.Smpd3,the gene encoding neutral sphingomyelinase,is identified as a new target gene directly regulated by HIF-1αthat is involved in ceramide generation.Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice.Therefore,HIF-1αinhibition may constitute a novel approach to slow atherosclerotic progression.

关键词： HIF-1a SMPD3 Ceramide PX-478 Adipocyte Cholesterol Inflammatory responses Atherosclerosis

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Room-temperature third-order nonlinear Hall effect in Weyl semimetal TalrTe4

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National Science Review 2022年第12期9卷 177-184页

作者： Cong Wang Rui-Chun Xiao huiying liu Zhaowei Zhang Shen Lai Chao Zhu Hongbing Cai Naizhou Wang Shengyao Chen Ya Deng Zheng liu Shengyuan A.Yang Wei-Bo Gao College of Mathematics and Physics Beijing University of Chemical Technology Division of Physics and Applied Physics School of Physical and Mathematical Sciences Nanyang Technological University Institute of Physical Science and Information Technology Anhui University Research Laboratory for Quantum Materials Singapore University of Technology and Design School of Materials Science and Engineering Nanyang Technological University CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology The Photonics Institute and Centre for Disruptive Photonic Technologies Nanyang Technological University

The second-order nonlinear Hall effect observed in the time-revers al symmetric system has not only shown abundant physical content,but also exhibited potential application prospects.Recently,a third-order nonlinear Hall effect has been observed in MoTe2and WTe2.However,few-layer MoTe2and WTe2are usually unstable in air and the observed third-order nonlinear Hall effect can be measured only at low temperature,which hinders further investigation as well as potential application.Thus,exploring new air-stable material systems with a sizable third-order nonlinear Hall effect at room temperature is an urgent task.Here,in type-Ⅱ Weyl semimetal TaIrTe4,we observed a pronounced third-order nonlinear Hall effect,which can exist at room temperature and remain stable for months.The third-order nonlinear Hall effect is connected to the Berry-connection polarizability tensor instead of the Berry curvature.The possible me chanism of the observation of the third-order nonlinear Hall effe ct in TaIrTe4at room temperature has been discussed.Our findings will open an avenue towards exploring room-temperature nonlinear devices in new quantum materials.

关键词： topological material third-order nonlinear Hall effect room temperature Berry connection polarizability tensor

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Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

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Regenerative Biomaterials 2016年第5期3卷 309-317页

作者： Shenglian Yao huiying liu Shukui Yu Yuanyuan Li Xiumei Wang Luning Wang School of Materials Science and Engineering University of Science and Technology BeijingBeijing 100083China State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084China Department of Oral and Maxillofacial Surgery School of StomatologyDalian Medical UniversityDalian 116044China Institute for Neuroscience Capital Medical UniversityBeijing 100069China

The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system.In this study,two kind of aqueous model drugs with different molecule weight,Congo red and albumin from bovine serum(BSA)were nanoencapsulated in poly(DL-lactic-co-glycolic acid)(PLGA)microspheres by emulsion electrospray.In the preparation process,the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution.The emulsion was then electrosprayed to fabricate drugnanoencapsulated PLGA microspheres.The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase(V_(w)/V_(o))and the molecule weight of model drugs.Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to V_(w)/V_(o).With the increase of the volume ratio of aqueous drug phase,the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate.Moreover,BSA showed a slower release rate from PLGA microspheres comparing to Congo red,which indicated the drug release rate could be affected by not only V_(w)/V_(o)but also the molecule weight of model drug.In brief,the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple systemto achieve controlled drug release at a desired rate satisfying the need of the practices.

关键词： PLGA microspheres drug nanoencapsulation emulsion electrospray controlled drug release

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Hierarchically electrospraying a PLGA@chitosan sphere-in-sphere composite microsphere for multi-drug-controlled release

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Regenerative Biomaterials 2020年第4期7卷 381-390页

作者： Zhu liu Weilong Ye Jingchuan Zheng Qindong Wang Guowu Ma huiying liu Xiumei Wang State Key Laboratory of New Ceramic&Fine Processing School of Materials Science and EngineeringTsinghua UniversityNo.1 QinghuayuanBeijing 100084China Department of Prosthodontics School of StomatologyDalian Medical UniversityNo.9 west sectionLvshunnan RoadDalian 116044China

Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration,which usually demands appropriate carriers like microspheres(MS)to control drugs releases.Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate.In this study,we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres,with smaller poly(lactic-co-glycolic acid)MS(~8-10 lm in diameter)embedded in a larger chitosan MS(~250-300 lm in diameter).The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage.Two kinds of model drugs,bovine serum albumin and chlorhexidine acetate,were encapsulated in the microspheres.The fluorescence-labeled rhodamine-fluoresceine isothiocyanate(Rho-FITC)and ultraviolet(UV)spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres,as well as sustained,slow release in vitro.In addition,far-UV circular dichroism and matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)results indicated original secondary structure and molecular weight of drugs after electrospraying.Generally speaking,our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded,which could be applied in sequential,multi-modality therapy.

关键词： PLGA chitosan electrospray composite microsphere

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Formation Energies of the Lithium Intercalations in MoS_2

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Journal of Materials Science & Technology 2006年第1期22卷 40-44页

作者： Aiyu LI huiying liu Zizhong ZHU Meichun HUANG Yong YANG Department of Physics Xiamen University Xiamen 361005 China Department of Physics Jimei University Xiamen 361021 China State Key Lab for Physical Chemistry of Solid Surfaces Xiamen University Xiamen 36100 China

第一原则的计算被执行了在 MoS_2 学习锂置闰。形成精力，体积的变化，电子结构和在 MoS_2 的锂置闰的费用密度被介绍。我们的计算证明在在 MoS_2 的锂置闰期间，锂置闰形成精力每锂原子在到 3.0 eV 的 2.5 eV 之间。MoS_2

关键词：生成能硫化锰锂从头计算法

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Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters

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Acta Pharmaceutica Sinica B 2019年第4期9卷 702-710页

作者： Lulu Sun Yuanyuan Pang Xuemei Wang Qing Wu huiying liu Bo liu George liu Min Ye Wei Kong Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking Universityand the Key Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences Ministry of EducationPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Since metabolic process differs between humans and mice, studies were performed in hamsters, which are generally considered to be a more appropriate animal model for studies of obesityrelated metabolic disorders. The modulation of gut microbiota, bile acids and the farnesoid X receptor(FXR) axis is correlated with obesity-induced insulin resistance and hepatic steatosis in mice. However,the interactions among the gut microbiota, bile acids and FXR in metabolic disorders remained largely unexplored in hamsters. In the current study, hamsters fed a 60% high-fat diet(HFD) were administeredvehicle or an antibiotic cocktail by gavage twice a week for four weeks. Antibiotic treatment alleviated HFD-induced glucose intolerance, hepatic steatosis and inflammation accompanied with decreased hepatic lipogenesis and elevated thermogenesis in subcutaneous white adipose tissue(sWAT). In the livers of antibiotic-treated hamsters, cytochrome P450 family 7 subfamily B member 1(CYP7 B1) in the alternative bile acid synthesis pathway was upregulated, contributing to a more hydrophilic bile acid profile with increased tauro-β-muricholic acid(TβMCA). The intestinal FXR signaling was suppressed but remained unchanged in the liver. This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.

关键词： Gut microbiota CYP7B1 TβMCA FXR Metabolic disorders

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Metabolic disorder in the progression of heart failure

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Science China(Life Sciences) 2019年第9期62卷 1153-1167页

作者： Xiuxiu Zhang huiying liu Juan Gao Min Zhu Yupeng Wang Changtao Jiang Ming Xu Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital/ NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of Education and Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.

关键词： heart failure metabolomics TAC HF stages A–C biomarker pathway analysis

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郑州地域文化融入高校思想政治教育应用研究

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开封文化艺术职业学院学报 2024年第2期44卷 61-65页

作者：刘慧莹河南牧业经济学院金融与会计学院河南郑州450000

优秀的地域文化蕴含着丰富的思想内涵和时代价值,是高校思想政治教育过程中重要的文化资源。郑州高校较多,地域文化资源丰富,有着厚重的文化底蕴和丰富的历史遗存。为此,以郑州地域文化为基础,从郑州地域文化融入高校思想政治教育的现... 详细信息

优秀的地域文化蕴含着丰富的思想内涵和时代价值,是高校思想政治教育过程中重要的文化资源。郑州高校较多,地域文化资源丰富,有着厚重的文化底蕴和丰富的历史遗存。为此,以郑州地域文化为基础,从郑州地域文化融入高校思想政治教育的现状入手,从加强政策规划、创新教学体系、培育特色校园文化等方面探析郑州地域文化融入高校思想政治教育、实现育人价值的有效路径,促进高校充分发挥文化育人功能。

关键词：郑州地域文化高校思想政治教育文化育人

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半夏泻心汤加减联合常规西药治疗脾虚胃热型慢性胃炎的临床效果

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中国社区医师 2024年第1期40卷 75-77页

作者：刘慧英北京市大兴区亦庄医院中医科北京100176

目的:分析半夏泻心汤加减联合常规西药治疗脾虚胃热型慢性胃炎的临床效果。方法:选取2021年11月—2022年11月北京市大兴区亦庄医院收治的76例脾虚胃热型慢性胃炎患者作为研究对象,以随机数字表分法分为对照组与观察组,各38例。对照组行... 详细信息

目的:分析半夏泻心汤加减联合常规西药治疗脾虚胃热型慢性胃炎的临床效果。方法:选取2021年11月—2022年11月北京市大兴区亦庄医院收治的76例脾虚胃热型慢性胃炎患者作为研究对象,以随机数字表分法分为对照组与观察组,各38例。对照组行常规西药治疗,观察组在对照组基础上应用半夏泻心汤加减治疗。比较两组中医证候积分、胃肠功能、超氧化物歧化酶(SOD)水平、炎性因子水平、不良反应发生情况。结果:治疗后,两组反酸、胃痛、胃脘痞闷积分及肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6水平低于治疗前,且观察组低于对照组,两组胃泌素、胃动素、SOD水平高于治疗前,且观察组高于对照组,差异有统计学意义(P0.05)。结论:半夏泻心汤加减联合常规西药治疗脾虚胃热型慢性胃炎的临床效果显著,能够减轻患者不适症状与炎性反应,改善胃肠功能,调节SOD水平,且安全性较高。

关键词：半夏泻心汤慢性胃炎不良反应

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Development of an antimicrobial peptide-loaded mineralized collagen bone scaffold for infective bone defect repair

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Regenerative Biomaterials 2020年第5期7卷 515-525页

作者： Yuzhu He Yahui Jin Xiaoxia Ying Qiong Wu Shenglian Yao Yuanyuan Li huiying liu Guowu Ma Xiumei Wang State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityZhongguancun StreetHaidian DistrictBeijing 100084China Department of Oral Prosthodontics School of StomatologyDalian Medical UniversityLvshun South RoadLushunkou DistrictDalian 116044China Department of Stomatology Zhejiang Provincial Hospital of Chinese MedicineThe 9th StreetEconomic and Technological Development ZoneHangzhou 310018China School of Life Sciences Tsinghua UniversityZhongguancun StreetHaidian DistrictBeijing 100084China

The repair of infective bone defects is a great challenge in clinical work.It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local anti-infection and bone regeneration.A porous mineralized collagen(MC)scaffold containing poly(D,L-lactide-co-glycolic acid)(PLGA)microspheres loaded with two antibacterial synthetic peptides,Pac-525 or KSL-W was developed and characterized via scanning electron microscopy(SEM),porosity measurement,swelling and mechanical tests.The results showed that the MC scaffold embedded with smooth and compact PLGA microspheres had a positive effect on cell growth and also had antibacterial properties.Through toxicity analysis,cell morphology and proliferation analysis and alkaline phosphatase evaluation,the antibacterial scaffolds showed excellent biocompatibility and osteogenic activity.The antibacterial property evaluated with Staphylococcus aureus and Escherichia coli suggested that the sustained release of Pac-525 or KSL-W from the scaffolds could inhibit the bacterial growth aforementioned in the long term.Our results suggest that the antimicrobial peptides-loaded MC bone scaffold has good antibacterial and osteogenic activities,thus providing a great promise for the treatment of infective bone defects.

关键词： antibacterial peptides PLGA microspheres mineralized collagen scaffold osteogenic differentiation

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