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Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15

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Current Medical Science 2023年第1期43卷 35-47页

作者： Ning JI Chong-guang WU Xiao-die WANG zhi-xue song Pei-yuan WU Xin LIU Xu FENG Xiang-mei ZHANG Xiu-fang WANG Zhan-jun LV Department of Genetics Hebei Medical UniversityHebei Key Lab of Laboratory AnimalShijiazhuang 050017China Research Center Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China

Objective:To investigate whether human short interspersed nuclear element antisense RNA(Alu antisense RNA;Alu asRNA)could delay human fibroblast senescence and explore the underlying mechanisms.Methods:We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8(CCK-8),reactive oxygen species(ROS),and senescence-associated beta-galactosidase(SA-β-gal)staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts.We also used an RNA-sequencing(RNA-seq)method to investigate the Alu asRNA-specific mechanisms of anti-aging.We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA.We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts.Results:The CCK-8,ROS and SA-β-gal results showed that Alu asRNA could delay fibroblast aging.RNA-seq showed 183 differentially expressed genes(DEGs)in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection(CPT)reagent.The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent.Notably,Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway.Conclusion:Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.

关键词： senescent fibroblast cell proliferation Alu antisense RNA KIF15 gene expression MEK-ERK signaling pathway cell cycle

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Alu antisense RNA ameliorates methylglyoxal-induced human lens epithelial cell apoptosis by enhancing antioxidant defense

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International Journal of Ophthalmology(English edition) 2023年第2期16卷 178-190页

作者： Pei-Yuan Wu Ning Ji Chong-Guang Wu Xiao-Die Wang Xin Liu zhi-xue song Murad Khan Suleman Shah Ying-Hua Du Xiu-Fang Wang Li-Fang Yan Department of Genetics Hebei Medical UniversityHebei Key Lab of Laboratory AnimalShijiazhuang 050017Hebei ProvinceChina Department of Ophthalmology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

AIM:To determine whether an antisense RNA corresponding to the human Alu transposable element(Aluas RNA)can protect human lens epithelial cells(HLECs)from methylglyoxal-induced apoptosis.METHODS:Cell counting kit-8(CCK-8)and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays were used to assess HLEC viability.HLEC viability/death was detected using a Calcein-AM/PI double staining kit;the annexin V-FITC method was used to detect HLEC apoptosis.The cytosolic reactive oxygen species(ROS)levels in HLECs were determined using a reactive species assay kit.The levels of malondialdehyde(MDA)and the antioxidant activities of total-superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px)were assessed in HLECs using their respective kits.RT-q PCR and Western blotting were used to measure m RNA and protein expression levels of the genes.RESULTS:Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxalinduced decrease in Bcl-2 m RNA and the methylglyoxalinduced increase in Bax m RNA.In addition,Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression.Aluas RNA inhibited the production of ROS induced by methylglyoxal,restored T-SOD and GSHPx activity,and moderated the increase in MDA content after treatment with methylglyoxal.Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes,including glutathione peroxidase,heme oxygenase 1,γ-glutamylcysteine synthetase and quinone oxidoreductase 1.Aluas RNA ameliorated methylglyoxal-induced increases of the m RNA and protein expression of Keap1 that is the negative regulator of Nrf2.CONCLUSION:Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense.

关键词： human Alu antisense RNA human lens epithelial cells methylglyoxal toxicity antioxidant defense apoptosis

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Open-Shell Oligomers and Polymers: Theory, Characterization Methods, Molecular Design, and Applications

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Chinese Journal of Polymer Science 2024年第4期42卷 417-436页

作者： xue-Qing Wang Cheng song Ting Lei Key Laboratory of Polymer Chemistry and Physics(Ministry of Education) School of Materials Science and EngineeringPeking UniversityBeijing100871China

Open-shell oligomers and polymers have exhibited intriguing electronic and magnetic properties, making them highly desirable for a wide range of applications, including ambipolar organic field-effect transistors (OFETs), photodetectors, organic thermoelectrics, and spintronics. Although open-shell ground states have been observed in certain small molecules and doped organic semiconductors, the exploration of open-shell ground-state conjugated polymers is still limited, and the strategies for designing these polymers remain obscure. This review aims to briefly introduce the theory and characterization methods of open-shell conjugated polymers, along with an overview of recent progress and applications. The objective is to stimulate further advancements and investigations in this promising area by shedding light on the potential of open-shell conjugated polymers and the challenges that lie ahead.

关键词： Conjugated polymers Open-shell molecules High-spin ground state Donor-acceptor(D-A)polymers Optoelectronic and magnetic properties

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Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion

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Protein & Cell 2024年第6期15卷 403-418页

作者： song xue Yuru Han Fan Wu Qiao Wang Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecurityShanghai Frontiers Science Center of Pathogenic Microorganisms and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032China

Intensive selection pressure constrains the evolutionary trajectory of SARS-CoV-2 genomes and results in various novel variants with distinct mutation profiles.Point mutations,particularly those within the receptor binding domain(RBD)of SARS-CoV-2 spike(S)protein,lead to the functional alteration in both receptor engagement and monoclonal antibody(mAb)recognition.Here,we review the data of the RBD point mutations possessed by major SARS-CoV-2 variants and discuss their individual effects on ACE2 affinity and immune evasion.Many single amino acid substitutions within RBD epitopes crucial for the antibody evasion capacity may conversely weaken ACE2 binding affinity.However,this weakened effect could be largely compensated by specific epistatic mutations,such as N501Y,thus maintaining the overall ACE2 affinity for the spike protein of all major variants.The predominant direction of SARS-CoV-2 evolution lies neither in promoting ACE2 affinity nor evading mAb neutralization but in maintaining a delicate balance between these two dimensions.Together,this review interprets how RBD mutations efficiently resist antibody neutralization and meanwhile how the affinity between ACE2 and spike protein is maintained,emphasizing the significance of comprehensive assessment of spike mutations.

关键词： ACE2 affinity maintained

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Dietary Macleaya cordata extract supplementation improves the growth performance and gut health of broiler chickens with necrotic enteritis

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Journal of Animal Science and Biotechnology 2024年第1期15卷 374-395页

作者： Bochen song Jie He xue Pan Linglian Kong Chuanpi Xiao Chake Keerqin zhigang song Key Laboratory of Efficient Utilization of Non‑Grain Feed Resources College of Animal Science and TechnologyShandong Agricultural UniversityTaian 271018ShandongChina Center for Mitochondria and Healthy Ageing College of Life SciencesYantai UniversityYantai 264005ShandongChina Precision Livestock and Nutrition Unit University of LiègeGembloux Agro‑Bio TechGemblouxBelgium Phytobiotics(Jiangsu)Biotech Co. Ltd.Jintan 213200China

Background The poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE)caused by Clostridium perfringens.Methods The aim of this study was to investigate the effects of dietary supplementation with Macleaya cordata extract(MCE)on the immune function and gut microbiota of broilers with NE.A total of 2881-day-old broiler chicks were randomly assigned to a 2×2 factorial arrangement with two concentrations of dietary MCE supplementation(0 or 350 mg/kg of diet)and two disease challenge statuses(control or NE).Results The results revealed that NE significantly increased the feed conversion rate(FCR),mortality,intestinal lesion score,the levels of IL-1β,IL-17 and IFN-γ/IL-4 in serum and IL-17/IL-10 in the jejunal mucosa,m RNA levels of TLR2,IFN-γand p Ig R in the jejunum,and Clostridium perfringens concentrations in the cecum.NE significantly decreased the body weight(BW),body weight gain(BWG),jejunal villus height,V/C,m RNA level of AMPK-α1 in jejunum,IL-4 level in the jejunal mucosa and lactic acid bacteria abundance in the cecum.MCE significantly increased BW,BWG,jejunal villus height,V/C,m RNA levels of occludin,ZO-1 and AMPK-α1 in the jejunum,the levels of Ig A and Ig G in serum and IL-10 in the jejunal mucosa and m RNA levels of NF-κB,IL-10 and MHC-II in the jejunum.Additionally,MCE significantly decreased the FCR,mortality,intestinal lesion score,jejunal crypt depth,the levels of IFN-γand IL-17 in serum and IL-17/IL-10 in the jejunal mucosa,Clostridium perfringens concentrations in the cecum,and m RNA levels of IL-17/IL-10 in the jejunum.Moreover,NE significantly increased the abundance of bacteria that are associated with inflammation,obesity and depression(Alistipes,Barnesiella,Intestinimonas,RF39 and UCG-005)and significantly decreased the abundance of short-chain fatty acid(SCFA)-producing bacteria(Anaerotruncus,Butyricicoccus and Bacteroides)in the cecum.MCE significantly increased the abundance of SCFA-producing bacteria(Streptococcus,Ruminococcus_torques_group

关键词： Broiler chicken Gut microbiota Immune function Macleaya cordata extract Necrotic enteritis

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Random Forest-Based Fatigue Reliability-Based Design Optimization for Aeroengine Structures

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Computer Modeling in Engineering & Sciences 2024年第7期140卷 665-684页

作者： xue-Qin Li Lu-Kai song School of Energy and Power Engineering Beihang UniversityBeijing100191China Department of Mechanical Engineering The Hong Kong Polytechnic UniversityKowloonHong Kong999077China Research Institute of Aero-Engine Beihang UniversityBeijing100191China

Fatigue reliability-based design optimization of aeroengine structures involves multiple repeated calculations of reliability degree and large-scale calls of implicit high-nonlinearity limit state function,leading to the traditional direct Monte Claro and surrogate methods prone to unacceptable computing efficiency and accuracy.In this case,by fusing the random subspace strategy and weight allocation technology into bagging ensemble theory,a random forest(RF)model is presented to enhance the computing efficiency of reliability degree;moreover,by embedding the RF model into multilevel optimization model,an efficient RF-assisted fatigue reliability-based design optimization framework is developed.Regarding the low-cycle fatigue reliability-based design optimization of aeroengine turbine disc as a case,the effectiveness of the presented framework is validated.The reliabilitybased design optimization results exhibit that the proposed framework holds high computing accuracy and computing efficiency.The current efforts shed a light on the theory/method development of reliability-based design optimization of complex engineering structures.

关键词： Random forest reliability-based design optimization ensemble learning machine learning

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Grain-boundary segregation and grain growth in nanocrystalline substitutional solid solution alloys

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Journal of Materials Science & Technology 2024年第1期168卷 239-249页

作者： Fawei Tang Chao Hou Hao Lu zhi Zhao Xiaoyan song Faculty of Materials and Manufacturing Key Laboratory of Advanced Functional MaterialsMinistry of Education of ChinaBeijing University of TechnologyBeijing 100124China

A model for describing solute segregation at grain boundaries has been developed for substitutional solid solution alloys,which integrates multiple factors from atomic to microstructural scales.A concept of mo-lar Gibbs free energy of segregation was introduced to evaluate the segregating capability of the solute elements in a closed system,through which the influences of grain boundary structure,grain size,ma-terial composition,and external conditions were described.Based on the evaluation of various energy forms related to solute segregation and grain growth processes,the nature of the thermal stabilization of nanograin structures by solute segregation was disclosed.A criterion for the destabilization of nanostruc-tures,which is determined by the competition of the change rates between the molar Gibbs free energy of segregation and the total energy of grain boundaries with grain size,has been proposed.This study provided guideline to achieve high-temperature stability of nanograin structures of solid solution alloys even for the weakly segregating nanocrystalline systems.

关键词： Substitutional solid solution Grain boundary segregation Thermal stabilization Solute concentration Grain size

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Mechanistic insight into Cr(Ⅵ)retention by Si-containing ferrihydrite

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Journal of Environmental Sciences 2024年第5期139卷 217-225页

作者： Ying Hu Qiang xue Honghan Chen Huaming Guo Kenneth C.Carroll song Wang MOE Key Laboratory of Groundwater Circulation and Environmental Evolution School of Water Resources and EnvironmentChina University of Geosciences(Beijing)Beijing 100083China Beijing Key Laboratory of Water Resources and Environmental Engineering School of Water Resources and EnvironmentChina University of GeosciencesBeijing 100083China State Key Laboratory of Biogeology and Environmental Geology China University of GeosciencesBeijing 100083China Plant&Environmental Science New Mexico State UniversityNM 88003USA Institute of Theoretical Chemistry College of ChemistryJilin UniversityChangchun 130023China

Hexavalent chromium[Cr(Ⅵ)]causes serious harm to the environment due to its high toxicity,solubility,and mobility.Ferrihydrites(Fh)are the main adsorbent and trapping agent of Cr(Ⅵ)in soils and aquifers,and they usually coexist with silicate(Si),forming Si-containing ferrihydrite(Si-Fh)mixtures.However,the mechanism of Cr(Ⅵ)retention by Si-Fh mixtures is poorly understood.In this study,the behaviors and mechanisms of Cr(Ⅵ)adsorption onto Si-Fh with different Si/Fe molar ratios was investigated.Transmission electron microscope,Fourier transform infrared spectroscopy,X-ray diffraction,X-ray photoelectron spectroscopy,and other techniques were used to characterize Si-Fh and Cr(Ⅵ)-loading of Si-Fh.The results show that specific surface area of Si-Fh increases gradually with increasing Si/Fe ratios,but Cr(Ⅵ)adsorption on Si-Fh decreases with increasing Si/Fe ratios.This is because with an increase in Si/Fe molar ratio,the point of zero charge of Si-Fh gradually decreases and electrostatic repulsion between Si-Fh and Cr(Ⅵ)increases.However,the complexation of Cr(Ⅵ)is enhanced due to the increase in adsorbed hydroxyl(A-OH-)on Si-Fh with increasing Si/Fe molar ratio,which partly counteracts the effect of the electrostatic repulsion.Overall,the increase in the electrostatic repulsion has a greater impact on adsorption than the additional complexation with Si-Fh.Density functional theory calculation further supports this observation,showing the increases in electron variation of bonding atoms and reaction energies of inner spherical complexes with the increase in Si/Fe ratio.

关键词： Hexavalent chromium Ferrihydrite Si/Fe ratio Cr(Ⅵ)Adsorption

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Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

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Biomedical and Environmental Sciences 2024年第2期37卷 178-186页

作者： song Yun HE Ying LU xue Xin ZHANG Xiao Mei JIANG XIAO Lin song Qing HUANG xue Yong MA Hong Xia YU Peng Cheng ZHU Wu Yang Henan Provincial Center for Disease Control and Prevention Infectious Disease Prevention and Control InstituteHenan Provincial Key Laboratory of Infectious Disease PathogensZhengzhou 450000HenanChina National Institute for Viral Disease Control and Prevention China CDCKey Laboratory of BiosafetyNational Health CommissionBeijing 102206China Shandong Provincial Center for Disease Control and Prevention Jinan 250014ShandongChina Qingdao Chengyang District Center for Disease Control and Prevention Qingdao 266108ShandongChina

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

关键词： Rabies Post-exposure immunization Essen regimen RVNAs

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Increasing operational stability of journal bearing in hydraulic suspension micro-pump by herringbone grooved structure

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Science China(Technological Sciences) 2024年第3期67卷 853-862页

作者： HONG Tao XING GuanYing ZUO HuaiYu xue song LUO XiaoBing State Key Laboratory of Coal Combustion School of Energy and Power EngineeringHuazhong University of Science and TechnologyWuhan 430074China

The operational stability of radial journal bearings is the bottleneck that limits the reliability of hydraulic suspension micropump. Due to self-excited vibrations, the whirl amplitude of the plain journal bearing(PJB) is large at high rotational speeds,which will accelerate wear failure. It has been proven that employing herringbone grooved journal bearing(HGJB) is an effective method to reduce the whirl amplitude and improve operational stability. However, enhancing the stability of journal bearings in micro-pumps by herringbone grooved structures has rarely been studied, and its effect needs to be verified. We validated the mechanism of the stability improvement with the CFD method and compared the dynamic characteristics of HGJB and PJB by rotor dynamics evaluation and experiment. The experimental results show that under the same conditions the whirl amplitude of the HGJB decreases by 29.61% in the x direction and by 24.09% in the y direction compared with that of the PJB. This study reveals the effect of the herringbone grooved structure on the operational stability of bearings and may provide guidance for the reliability improvement of hydraulic suspension micro-pump.

关键词： journal bearing herringbone groove hydrodynamic effect micro-pump

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