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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang xiaoyi liu Jiajie Kuai Fengling Wang Wei Wei Institute of Clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of Clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex etiology.Monocyte-derived macrophages(MDMs)infiltration are associated with RA severity.We have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling.However,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been understudied.Thus,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)mice.Synovial inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)mice.Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting protein.We further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγsignaling.Mechanistically,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 transcription.Furthermore,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and angiogenesis.Altogether,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling.Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Dynamic response of buildings under debris flow impact

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Journal of Mountain Science 2024年第5期21卷 1581-1597页

作者： liu Huan FAN xiaoyi TIAN Shujun DENG Xin School of Mechanical and Electrical Engineering Southwest Petroleum UniversityChengdu 610500China School of Civil Engineering and Geomatics Southwest Petroleum UniversityChengdu 610500China Housing and Urban-Rural Development Bureau of Mingshan District Ya’an 625100China Engineering Safety Assessment and Protection Research Southwest Petroleum UniversityChengdu 610500China School of Civil Engineering and Architecture Southwest University of Science and TechnologyMianyang 621010China

This study employs the smoothed particle hydrodynamics–finite element method(SPH–FEM) coupling numerical method to investigate the impact of debris flow on reinforced concrete(RC)-frame buildings. The methodology considers the variables of debris flow depth and velocity and introduces the intensity index IDV(IDV = DV) to evaluate three different levels of debris flow impact intensity. The primary focus of this study is to investigate the dynamic response and failure mechanism of RC-frame buildings under debris flow impact, including structural failure patterns, impact force and column displacement. The results show that under a highintensity impact, a gradual collapse process of the RCframe building can be observed, and the damage mode of the frame column reflects shear failure or plastic hinge failure mechanism. First, the longitudinal infill walls are damaged owing to their low out-of-plane flexural capacity;the critical failure intensity index IDV value is approximately 7.5 m2/s. The structure cannot withstand debris flows with an intensity index IDV greater than 16 m2/s, and it is recommended that the peak impact force should not exceed 2100 k N. The impact damage ability of debris flow on buildings mostly originates from the impact force of the frontal debris flow, with the impact force of the debris flow body being approximately 42% lower than that of the debris flow head. Finally, a five-level classification system for evaluating the damage status of buildings is proposed based on the numerical simulation and investigation results of the disaster site.

关键词： SPH–FEM method Debris flow Buildings The intensity index Dynamic response

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Hexamerin and allergen are required for female reproduction in the American cockroach,Periplaneta americana

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Insect Science 2024年第1期31卷 186-200页

作者： Shiming Zhu xiaoyi Chen Sishi Xia Qin Li Ziqi Ye Shaoting Zhao Kexin liu Fangfang liu Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Institute of Insect Science and TechnologyInstitute of Insect Science and Technology&School of Life SciencesSouth China Normal UniversityGuangzhouChina Guangmeiyuan R&D Center Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied TechnologySouth China Normal UniversityMeizhouGuangdong ProvinceChina Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural UniversityGuangzhouChina

Reproduction is of great importance for the continuation of the species.In insects,the fat body is the major tissue for nutrient storage and involved in vitellogenesis,which is essential for female reproduction.Here,2 proteins,hexamerin and allergen,were separated from the fat bodies of adult female American cockroaches(Periplaneta americana)and identified as storage proteins,encoding for 733 amino acids with molecular weight of 87.88 kDa and 686 amino acids with molecular weight of 82.18 kDa,respectively.The encoding genes of these 2 storage proteins are mainly expressed in the fat body.RNA interference-mediated knockdown of Hexamerin and Allergen in the early stage of the first reproductive cycle in females suppressed vitellogenesis and ovarian maturation,indicating that these storage proteins are involved in controlling reproduction.Importantly,the expression of Hexamerin and Allergen was repressed by knockdown of the juvenile hormone(JH)receptor gene Met and the primary response gene Kr-h1,and was induced by methoprene,a JH analog,in both in vivo and in vitro experiments.Altogether,we have determined that hexamerin and allergen are identified as storage proteins and play an important role in promoting female reproduction in the American cockroach.The expression of their encoding genes is induced by JH signaling.Our data reveal a novel mechanism by which hexamerin and allergen are necessary for JH-stimulated female reproduction.

关键词： fat body juvenile hormone ovary reproduction storage protein vitellogenesis

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Eutectogel-based self-powered wearable sensor for health monitoring in harsh environments

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Nano Research 2024年第6期17卷 5559-5568页

作者： Junpeng Wu Xinru Teng Lu liu Hongzhi Cui xiaoyi Li College of Materials Science and Engineering Ocean University of ChinaQingdao 266100China Key Lab for Special Functional Materials of Ministry of Education School of Materials Science and EngineeringHenan UniversityKaifeng 475004China

Triboelectric nanogenerators(TENG)have emerged as a highly promising energy harvesting technology,attracting significant attention in recent years for their broad applications.Gel-based TENGs,with superior stretchability and sensitivity,have been widely reported as wearable sensors.However,the traditional hydrogel-based TENGs suffer from freezing at low temperatures and drying at high temperatures,resulting in malfunctions.In this study,we introduce an anti-freezing eutectogel,which uses a deep eutectic solvent(DES),to improve the stability and electrical conductivity of TENGs in harsh environmental conditions.The eutectogel-based TENG(E-TENG)produces an open-circuit voltage of 776 V,a short-circuit current of 1.54μA,and a maximum peak power of 1.1 mW.Moreover,the E-TENG exhibits exceptional mechanical properties with an elongation at a break of 476%under tension.Importantly,it maintains impressive performances across a wide temperature range from−18 to 60℃,with conductivities of 2.15 S/m at−10℃and 1.75 S/m at−18℃.Based on the excellent weight stability of the E-TENG sensor,motion sensing can be achieved in the air,and even underwater.Finally,the versatility of the E-TENG can serve as a wearable sensor,by integrating it with Bluetooth technology.The self-powered E-TENG can monitor various human motion signals in real-time and send the health signals directly to mobile phones.This research paves a new road for the applications of TENGs in harsh environments,offering wireless flexible sensors with real-time health signal monitoring capabilities.

关键词： triboelectric nanogenerators self-powered harsh environment health monitoring Eutectogel

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Regulation of the pore structure of carbon nanosheets based electrocatalyst for efficient polysulfides phase conversions

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Journal of Materials Science & Technology 2024年第4期171卷 37-46页

作者： Xiaoyang liu Jingbo Zhang Kangli liu Shijie Zhang Rouhan Hou xiaoyi Hu Peng Zhang Guosheng Shao State Center for International Cooperation on Designer Low-Carbon&Environmental Materials(CDLCEM) School of Materials Science and EngineeringZhengzhou UniversityZhengzhou 450001China Zhengzhou Materials Genome Institute(ZMGI) Xingyang 450100China

The practical applications of lithium-sulfur(Li-S)batteries are hampered by the sluggish redox kinetics and polysulfides shuttle in the cyclic process,which leads to a series of problems including the loss of active materials and poor cycling efficiency.In this paper,the pore structures of carbon nanosheets based electrocatalysts were precisely controlled by regulating the content of water-soluble KCl template.The relationship between pore structures and Li-S electrochemical behavior was studied,which demonstrates a key influence of pore structure in polysulfides phase conversions.In the liquid-sloid redox reaction of polysulfides,the micropores and small mesopores(d20 nm)and macropores played a decisive role.As a typical exhibition,the nickel-embedded carbon nanosheets(Ni-CNS)with a high content of large mesopores and macropores can aid Li-S batteries in exhibiting stable cycling performance(760.1 mAh g^(-1)at 1 C after 300 cycles)and superior rate capac-ity(847.8 mAh g^(-1)at 2 C).Furthermore,even with high sulfur loading(8 mg cm^(−2))and low electrolyte(E/S is around 6μL mg^(-1)),the high area capacity of 7.7 mAh cm^(−2)at 0.05 C could be achieved.This work can provide a guideline for the design of the pore structure of carbon-based electrocatalysts toward high-efficiency sulfur species redox reactions,and afford a general,controllable,and simple approach to constructing high performance Li-S batteries.

关键词： Hierarchical porous carbon network Electrocatalyst Molten salt templating method Modified separators Li-S batteries

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A functional gel polymer electrolyte based on PVDF-HFP/gelatin toward dendrite-free lithium metal batteries

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Nano Research 2024年第4期17卷 2790-2799页

作者： xiaoyi Hu Kangli liu Shijie Zhang Guosheng Shao S.Ravi P.Silva Peng Zhang State Center for International Cooperation on Designer Low-carbon and Environmental Materials(CDLCEM) School of Materials Science and EngineeringZhengzhou UniversityZhengzhou 450001China Zhengzhou Materials Genome Institute(ZMGI) ZhongyuanzhiguXingyang 450100China Nanoelectronics Center Advanced Technology InstituteUniversity of SurreyGuildfordGU27XHUK

The leakage of liquid electrolyte and the formation of lithium dendrites pose challenges to safety and stability of lithium metal batteries(LMBs).The appearance of gel polymer electrolyte(GPE)has obviously improved the safety of traditional LMBs.However,the limited inhibition of GPE on lithium dendrites is detrimental to the safety of LMBs.Herein,a kind of poly(vinylidene fluoride-co-hexafluoropropylene)(PVDF-HFP)/gelatin(GN)GPE with high ionic conductivity,high-temperature resistance,and flame-retardancy,was prepared by electrospinning and soaking method.Utilizing the electrospinning network of PVDF-HFP,its affinity to liquid electrolytes,makes this GPE more beneficial to ions transport and the formation of gel.And,the GN with sol–gel properties,enhances the mechanical property(13.5 MPa)of HFP-GN GPE.Meanwhile,X-ray photoelectron spectroscopy(XPS)and density functional theory(DFT)suggest that the attraction of polar groups of GN to Li+can regulate the distribution of Li+and protect Li anodes.Consequently,the application of HFP-GN GPEs to LMBs with cathodes of LiFePO_(4) and LiCoO_(2) deliver excellent electrochemical performances:after 300 cycles,the LiFePO_(4)/HFP-GN GPE/Li battery keeps a low capacity decay rate of 0.09%at 5 C;after 400 cycles at 2 C,the LiCoO_(2)/HFP-GN GPE/Li cell retains a high capacity retention of 74%.This GPE is demonstrated for the application prospect of safe LMBs.

关键词： poly(vinylidene fluoride-co-hexafluoropropylene)(PVDF-HFP) gelatin polar groups lithium metal battery lithium dendrite

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Solid-state synthesis and ion transport characteristics of theβ-KSbF_(4)for all-solid-state fluoride-ion batteries

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Journal of Energy Chemistry 2024年第7期94卷 758-767页

作者： Jiali liu Huahui Zhao Jingcheng Xia Lingguang Yi xiaoyi Chen Dongdu Li Shuhan Ni Xinyi Su Yixuan Chen Min liu Xianyou Wang National Base for International Science&Technology Cooperation National Local Joint Engineering Laboratory for Key Materials of New Energy Storage BatteryHunan Province Key Laboratory of Electrochemical Energy Storage&ConversionSchool of ChemistryXiangtan UniversityXiangtan 411105HunanChina College of New Energy Ningbo University of TechnologyNingbo 315336ZhejiangChina

All-solid-state fluoride ion batteries(FIBs)have been recently considered as a post-lithium-ion battery system due to their high safety and high energy density.Just like all solid-state lithium batteries,the key to the development of FIBs lies in room-temperature electrolytes with high ionic conductivity.β-KSbF_(4)is a kind of promising solid-state electrolyte for FIBs owing to its rational ionic conductivity and relatively wide electrochemical stability window at room temperature.However,the previous synthesis routes ofβ-KSbF_(4)required the use of highly toxic hydrofluoric acid and the ionic conductivity of as-prepared product needs to be further improved.Herein,the β-KSbF_(4)sample with an ionic conductivity of 1.04×10^(-4)s cm^(-1)(30°C)is synthesized through the simple solid-state route.In order to account for the high ionic conductivity of the as-synthesizedβ-KSbF_(4),X-ray diffraction(XRD),scanning electron microscopy(SEM),and energy dispersive X-ray spectroscopy(EDS)are used to characterize the physic-ochemical properties.The results show that the as-synthesizedβ-KSbF_(4)exhibits higher carrier concentra-tion of 1.0×10^(-6)S cm-Hz^(-1)K and hopping frequency of 1.31×10^(6)Hz at 30°C due to the formation of the fluorine vacancies.Meanwhile,the hopping frequency shows the same trend as the changes of ionic conductivity with the changes of temperature,while the carrier concentration is found to be almost con-stant.The two different trends indicate the hopping frequency is mainly responsible for the ionic conduc-tion behavior withinβ-KSbF_(4).Furthermore,the all-solid-state FIBs,in which Ag and Pb+PbF_(2)are adopted as cathode and anode,andβ-KSbF_(4)as fluoride ion conductor,are capable of reversible charge and discharge.The assembled FIBs show a discharge capacity of 108.4 mA h g^(-1)at 1st cycle and 74.2 mA h g^(-1)at 50th cycle.Based on an examination of the capacity decay mechanism,it has been found that deterioration of the electrolyte/electrode interface is an important reason for hindering the commer-c

关键词： Solid-state electrolyte Carrier concentration Hopping frequency β-KSbF_(4) All-solid-state fluoride ion batteries

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Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

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Animal Models and Experimental Medicine 2024年第1期7卷 24-35页

作者： Xiaojun Deng xiaoyi Hu Shang Wang Hui Zhao Yaqin Wei Jiaqi Fu Wenhui Wu Jinming liu Caicai Zhang Lili Wang Ping Yuan Department of Critical Care Medicine Shanghai Sixth People's HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of Physiology Hainan Medical University HaikouHainanChina Department of Clinical Medical Laboratory Center Hangzhou Red Cross HospitalZhejiangChina

Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

关键词： brain microvascular endothelial cells exosomes Hes1 miR-9 neural stem cells

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Two Energy-Preserving Compact Finite Difference Schemes for the Nonlinear Fourth-Order Wave Equation

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Communications on Applied Mathematics and Computation 2022年第4期4卷 1509-1530页

作者： xiaoyi liu Tingchun Wang Shilong Jin Qiaoqiao Xu School of Mathematics and Statistics Nanjing University of Information Science and TechnologyNanjing 210044JiangsuChina

In this paper,two fourth-order compact finite difference schemes are derived to solve the nonlinear fourth-order wave equation which can be viewed as a generalized model from the nonlinear beam equation.Differing from the existing compact finite difference schemes which preserve the total energy in a recursive sense,the new schemes are proved to per-fectly preserve the total energy in the discrete sense.By using the standard energy method and the cut-off function technique,the optimal error estimates of the numerical solutions are established,and the convergence rates are of O(h^(4)+τ^(2))with mesh-size h and time-step τ.In order to improve the computational efficiency,an iterative algorithm is proposed as the outer solver and the double sweep method for pentadiagonal linear algebraic equations is introduced as the inner solver to solve the nonlinear difference schemes at each time step.The convergence of the iterative algorithm is also rigorously analyzed.Several numerical results are carried out to test the error estimates and conservative properties.

关键词： Nonlinear fourth-order wave equation Compact finite difference scheme Error estimate Energy conservation Iterative algorithm

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CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

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Animal Models and Experimental Medicine 2024年第3期7卷 310-323页

作者： xiaoyi Hu Shang Wang Hui Zhao Yaqin Wei Ruowang Duan Rong Jiang Wenhui Wu Qinhua Zhao Sugang Gong Lan Wang Jinming liu Ping Yuan Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of Geriatrics Shanghai Institute of GeriatricsHuadong HospitalFudan UniversityShanghaiChina Department of Anesthesiology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

关键词： circular postmeiotic segregation 1 circular RNAs hypoxia pulmonary hypertension vascular cells

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