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Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation

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Chinese Journal of Natural Medicines 2023年第2期21卷 127-135页

作者： LI Suping XU Fei Yu Liang yu Qian yu Nengwei FU Jing Department of Neurology Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072China Department of Rehabilitation Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072China

Stigmasterol is a plant sterol with anti-apoptotic,anti-oxidative and anti-inflammatory effect through multiple mechanisms.In this study,we further assessed whether it exerts protective effect on human brain microvessel endothelial cells(HBMECs)against ischemia-reperfusion injury and explored the underlying mechanisms.HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion(OGD/R)model,while a middle cerebral artery occlusion(MCAO)model of rats were constructed.The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance(SPR)and cellular thermal shift assay(CETSA).The results showed that 10μmol·L−1 stigmasterol significantly protected cell viability,alleviated the loss of tight junction proteins and attenuated the blood-brain barrier(BBB)damage induced by OGD/R in the in vitro model.Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites,including T692,a critical gatekeep residue of this receptor.Exogenous ephrin-A1(an EPHA2 ligand)exacerbated OGD/R-induced EPHA2 phosphorylation at S897,facilitated ZO-1/claudin-5 loss,and promoted BBB leakage in vitro,which were significantly attenuated after stigmasterol treatment.The rat MCAO model confirmed these protective effects in vivo.In summary,these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability,reducing the loss of tight junction proteins,and attenuating the BBB damage.These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

关键词： Stigmasterol Oxygen and glucose deprivation/reperfusion EPHA2 Blood-brain barrier

Study of the Combustion Process inside an Ethanol-Diesel Dual Direct Injection Engine Based on a Non-Uniform Injection Approach

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Fluid Dynamics & Materials Processing 2021年第1期17卷 159-170页

作者： Liying Zhou Yu Liang School of Mechanical Engineering Guizhou Institute of TechnologyGuiyang550003China School of Mechanical Engineering Guiyang UniversityGuiyang550005China

The use of ethanol is a promising method to reduce the emissions of diesel engines.The present study has been based on the installation of a gasoline electronic injection system in a single-cylinder diesel engine to control the amount of ethanol entering the cylinder during the compression(while diesel has been injected into the cylinder by the original pump injection system).The injection time has been controlled by crank angle signal collected by an AVL angle indicator.In the tests ethanol and diesel each accounted for half of the fuel volume,and the total heat energy supply of the fuel was equivalent to that of the diesel under the operating conditions of the original engine.A three-dimensional combustion model of the diesel engine has been implemented by using the CFD software FIRE.Simulations have been carried out assuming uniform and non-uniform injections rate for the different holes and the different results have been compared.According to these results,a non-uniform injection rate can produce early ignition and cause an increase in the maximum in-cylinder pressure and the maximum average incylinder temperature.Moreover,in such conditions NO emissions are larger while soot emission is slightly lower.

关键词： Combustion process dual direct injection diesel ethanol injection rate

A stable biocompatible porous coordination cage promotes in vivo liver tumor inhibition

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Nano Research 2021年第10期14卷 3407-3415页

作者： Yu Liang yu Fang Yong Cui Hongcai Zhou State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and State Key Laboratory of Metal Matrix CompositesShanghai Jiao Tong UniversityShanghai 200240China Department of Chemistry Texas A&M UniversityCollege StationTX 77843USA

Many emerging strategies in chemo-,gene-,and immunotherapy require the accumulation of reagents in the cell nucleus.However,their delivery into the nucleus is often limited.Nuclear delivery could be enhanced with a rationally designed cargo-delivery scaffold,but this approach has rarely been successfully implemented.Herein,a stable,biocompatible molecular capsule that encapsulates and delivers camptothecin,a DNA topoisomerase I inhibitor,into the nucleus of living cells was reported.Nuclear delivery is facilitated by the ultra-small diameter,zero net charge,and hydrophobicity of the capsule.The encapsulated drug complex displays superior toxicity towards multiple cancer cells over the free drug,the Food and Drug Administration(FDA)approved drugs,as well as conventionally reported drug vectors.Additionally,it inhibits liver cancer tumor growth in a xenograft mouse model.Modification of the properties of such molecular capsules may make it possible to design therapeutic strategies that target specific cell organelles.

关键词： metal-organic polyhedron biocompatible cage compound cavity drug delivery

Mitigating ROP Attacks via ARM-Specific In-Place Instruction Randomization

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China Communications 2016年第9期13卷 208-226页

作者： Yu Liang Key Laboratory of Aerospace Information Security and Trust Computing of Ministry of Education Wuhan 430079China Computer School of Wuhan University Wuhan 430079China

Defending against return-oriented programing(ROP) attacks is extremely challenging for modern operating systems.As the most popular mobile OS running on ARM,Android is even more vulnerable to ROP attacks due to its weak implementation of ASLR and the absence of effective control-flow integrity enforcement.In this paper,leveraging specific ARM features,an instruction randomization strategy to mitigate ROP attacks in Android even with the threat of single pointer leakage vulnerabilities is proposed.By popping out more registers in functions' epilogue instructions and reallocating registers in function scopes,branch targets in all(direct and indirect) branch instructions potential to be ROP gadgets are changed randomly.Without the knowledge of binaries' runtime instructions layout,adversary's repeated control flow transfer in ROP exploits will be subverted.Furthermore,this instruction randomization idea has been implemented in both Android Dalvik runtime and ART.Corresponding evaluations proved it is capable to introduce enough randomness for more than 99% discovered functions and thwart about 95% ROP gadgets in application's shared libraries and oat file compiled from Dalvik bytecode.Besides,evaluations on real-world exploits also confirmed its effectiveness on mitigating ROP attacks within acceptable performance overhead.

关键词： ROP 随机化 ARM 攻击指令配置寄存器现代操作系统移动操作系统

Analysis and experimental study on resistance-increasing behavior of composite high efficiency autonomous inflow control device

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PETROLEUM SCIENCE 2024年第2期21卷 1290-1304页

作者： Dong, liang-liang Zhang, yu-Lin Southwest Petr Univ Sch Mechatron Engn Chengdu 610500 Sichuan Peoples R China Southwest Petr Univ State Key Lab Oil & Gas Reservoir Geol & Exploitat Chengdu 610500 Sichuan Peoples R China Oil & Gas Equipment Technol Sharing & Serv Platfor Chengdu 610500 Sichuan Peoples R China

Bottom water coning is the main reason to reduce the recovery of horizontal bottom water reservoir. By water coning, we mean the oil-water interface changes from a horizontal state to a mound-shaped cone and breaks through to the wellbore. Autonomous inflow control device (AICD) is an important instrument maintain normal production after bottom water coning, however, the resistance increasing ability of the swirl type AICD is insufficient at present, which seriously affects the water control effect. Aiming this problem, this paper designs a multi-stage resistance-increasing and composite type AICD. The separation mechanism of oil-water two phases in this structure, the resistance form of oil-water single phase and the resistance-increasing principle of water phase are analyzed. Establishing the dual-phase multi-stage separation and resistance-increasing model, and verified by measuring the throttling pressure drop and oil-water volume fraction of the AICD, it is found that the composite type AICD has the effect of ICD and AICD at the same time, which can balance the production rate of each well section at the initial stage of production, delay the occurrence of bottom water coning. In the middle and later stages of production, water-blocking can be effectively increased to achieve water control and stable production. After structural sensitivity analysis, the influence law of various structural parameters on the water control performance of composite AICD was obtained. The simulation calculation results show that, compared with the existing swirl type AICD, composite AICD has higher sensitivity to moisture content, the water phase throttling pressure drop is increased by 4.5 times on average. The composite AICD is suitable for the entire stage of horizontal well production. (c) 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/ 4.0/).

关键词： Water control Flow separation Flow resistance-increasing AICD device Simulation and experiment DESIGN

REVA as A Well-curated Database for Human Expressionmodulating Variants

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Genomics, Proteomics & Bioinformatics 2021年第4期19卷 590-601页

作者： yu Wang Fang-yuan Shi Yu Liang Ge Gao State Key Laboratory of Protein and Plant Gene Research School of Life SciencesBiomedical Pioneering Innovation Center(BIOPIC)&Beijing Advanced Innovation Center for Genomics(ICG)Center for Bioinformatics(CBI)Peking UniversityBeijing 100871China Human Aging Research Institute School of Life SciencesNanchang UniversityNanchang 330031.China

More than 90%of disease-and trait-associated human variants are noncoding.By systematically screening multiple large-scale studies,we compiled REVA,a manually curated database for over 11.8 million experimentally tested noncoding variants with expression-modulating potentials.We provided 2424 functional annotations that could be used to pinpoint the plausible regulatory mechanism of these variants.We further benchmarked multiple state-of-the-art computational tools and found that their limited sensitivity remains a serious challenge for effective large-scale analysis.REVA provides high-quality experimentally tested expression-modulating variants with extensive functional annotations,which will be useful for users in the noncoding variant community.REVA is freely available at http://***.

关键词： Noncoding variant Expression-modulating variant Massively parallel reporter assay Database Benchmark

Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1903-1913页

作者： Ziru yu Dewen Kong Yu Liang Xiaoyue Zhao Guanhua Du State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of Drug Target and Screening ResearchInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Nicotinicα4β2 receptor antagonists have drawn increasing attention in the development of new antidepressants.In this study,we aimed to investigate the protective effect of VMY-2-95,the new selective antagonist ofα4β2 nicotinic acetylcholine receptor(nAChR)on corticosterone(CORT)injured mice and cellular models.Fluoxetine was applied as a positive control,and the effects of VMY-2-95 were investigated with three different doses or concentrations(1,3,10 mg/kg in mice,and 0.003,0.03,0.1μmol/L in cells).As a result,VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function,promoting hippocampal nerve proliferation,and regulating the contents of monoamine transmitters.Meanwhile,VMY-2-95 exhibited protective effects on cell viability,cell oxidant,cell apoptosis,and mitochondrial energy metabolism on corticosterone-impaired SH-SY5 Y cells.Also,the PKA-CREB-BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo,and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly.Therefore,we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5 Y cells against injuries induced by corticosterone.This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression.This study also supported the development ofα4β2 nAChR antagonists towards neuropsychiatric dysfunctions.

关键词： α4β2 nAChR antagonist VMY-2-95 Cholinergiceadrenergic theory Depression Corticosterone SH-SY5Y cells PKA-CREB-BDNF signaling pathway

Lignin derived absorbent for efficient and sustainable CO_(2) capture

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Chinese Journal of Chemical Engineering 2023年第2期54卷 89-97页

作者： yuandong Cui Bin He yu Lei Yu Liang Wanting Zhao Jian Sun Xiaomin Liu School of Chemistry and Chemical Engineering Qingdao UniversityQingdao 266071China School of Life Science Beijing Institute of TechnologyBeijing 100081China Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information TechnologyBeijing Engineering Research Center of Cellulose and Its DerivativesAdvanced Research Institute of Multidisciplinary ScienceBeijing Institute of TechnologyBeijing 100081China

High and cost-efficient capture of CO_(2) is a prerequisite and an inevitable path of carbon emission reduction. To address the challenges(high cost, low efficiency, less sustainability, etc.) of existing petroleum-based CO_(2) absorbents, herein, a class of efficient and sustainable lignin-based absorbents were resoundingly prepared by grafting the active amine group on a lignin derived compound vanillin and alkali lignin. The results demonstrated that vanillin modified by acrylamide achieved the excellent absorption capacity among the three absorbents, whose ability was 0.114 g CO_(2) per gram of absorbent under 25 ℃ and 100 kPa. In addition, the absorbent retained stable absorbability of CO_(2) after 6 cycles.The absorbing capacity of the absorbent formed by the coupling of vanillin and acrylamide to CO_(2) was much greater than their own(i.e. 0 g CO_(2) ·g^(-1)vanillin, 0.01 g CO_(2) ·g^(-1) acrylamide, respectively).Detailed information revealed the multi-site synergistic absorption mechanism, in which CO_(2) has C and O double interactions with the amide group of the absorbent, and single interaction with the hydroxyl oxygen on the benzene ring of the absorbent. The absorption capacity of modified lignin for CO_(2) is as high as 0.12 g CO_(2) per gram of absorbent, which is comparable with that of model compound vanillin.This work not only provides a new idea for the design of bio-absorbents for CO_(2) capture, but explores the application potential of lignin-based materials.

关键词： Lignin(model compound) CO_(2)absorption Amide group Multi-site Acid-base Hydrogen bonding

Author correction to‘Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models’[Acta Pharmaceutica Sinica B 11(2021)1903-1913]

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Acta Pharmaceutica Sinica B 2023年第2期13卷 899-901页

The authors regret that there was a picture error in Fig.5F owing to the inappropriate data statistics—forgetting gating when data collecting and a picture error in Fig.6F owing to the data copy mistake when drawing ... 详细信息

关键词： correction injuries getting