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Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase

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Chinese Journal of Natural Medicines 2024年第6期22卷 486-500页

作者： YANG Yanqiu CHE Yue FANG Mingxia YAO Xiaohu ZHOU Di WANG Feng CHEN Gang LIANG Dong LI Ning HOU Yue Key Laboratory of Bioresource research and Development of Liaoning Province College of Life and Health SciencesNorth-eastern UniversityShenyang 110000China National Frontiers Science center for Industrial Intelligence and Systems Optimization Key Laboratory of Data Analytics and Optimization for Smart IndustryMinistry of EducationNortheastern UniversityShenyang 110000China School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning provinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110000China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and Pharmaceutical SciencesGuangxi Normal UniversityGuilin 541000China

Neuroinflammation,mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3(NLRP3)inflammasome,is a significant contributor to the pathogenesis of neurodegenerative diseases(NDDs).Reynos-in,a natural sesquiterpene lactone(SL),exhibits a broad spectrum of pharmacological effects,suggesting its potential therapeutic value.However,the effects and mechanism of reynosin on neuroinflammation remain elusive.The current study explores the effects and mechanisms of reynosin on neuroinflammation using mice and BV-2 microglial cells treated with lipopolysaccharide(LPS).Our findings reveal that reynosin effectively reduces microglial inflammation in vitro,as demonstrated by decreased CD11b expression and lowered interleukin-1 beta(IL-1β)and interleukin-18(IL-18)mRNA and protein levels.Correspondingly,in vivo,results showed a re-duction in the number of Iba-1 positive cells and alleviation of morphological alterations,alongside decreased expressions of IL-1βand IL-18.Further analysis indicates that reynosin inhibits NLRP3 inflammasome activation,evidenced by reduced transcription of NLRP3 and caspase-1,diminished NLRP3 protein expression,inhibited apoptosis-associated speck-like protein containing a CARD(ASC)oli-gomerization,and decreased caspase-1 self-cleavage.Additionally,reynosin curtailed the activation of nicotinamide adenine dinuc-leotide phosphate(NADPH)oxidase,demonstrated by reduced NADP^(+)and NADPH levels,downregulation of gp91^(phox) mRNA,pro-tein expression,suppression of p47^(phox) expression and translocation to the membrane.Moreover,reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in vitro.These collective findings underscore reynosin’s capacity to mitigate mi-croglial inflammation by inhibiting the NLRP3 inflammasome,thus highlighting its potential as a therapeutic agent for managing neuroinflammation.

关键词： Microglia NLRP3 inflammasome Reactive oxygen species NADPH oxidase Neuron Reynosin

Observation on the aerosol and ozone precursors in suburban areas of Shenzhen and analysis of potential source based on MAX-DOAS

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Journal of Environmental Sciences 2023年第10期132卷 109-121页

作者： Hairong Zhang Ang Li Zhaokun Hu Hongmei Ren Hongyan Zhong Jianfeng Guo Long Yun Mingdi Zhang Key Laboratory of Environmental optics and Technology Anhui Institute of Optics and Fine MechanicsHefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China University of Science and Technology of China Hefei 230026China Institutes of Physical Science and Information Technology Anhui UniversityHefei 230601China Shenzhen Environmental Monitoring center Station Shenzhen 518049China

Long-term stereoscopic observations of aerosol,NO2,and HCHO were carried out at the Yangmeikeng(YMK)site in Shenzhen.Aerosol optical depths and NO2 vertical column concentration(NO2 VCD)derived from MAX-DOAS were found to be consistent with other datasets.The total NO2 VCD values of the site remained low,varying from 2×10^(15)to 8×10^(15)mol/cm^(2),while the HCHO VCD was higher than NO2 VCD,varying from 7×10^(15)to 11×10^(15)mol/cm^(2).HCHO VCD was higher from September to early November than that was from mid-late November to December and during February 2021,in contrast,NO2 VCD did not change much during the same period.In January,NO2 VCD and HCHO VCD were both fluctuating drastically.High temperature and HCHO level in the YMK site is not only driving the ozone production up but alsomay be driving up the ozone concentration as well,and the O_(3)production regime in the YMK site tends to be NOx-limited.At various altitudes,backward trajectory clustering analysis and Potential Source Contribution Function(PSCF)were utilized to identify possible NO2 and HCHO source locations.The results suggested that the Huizhou-Shanwei border and the Daya Bay Sea area were the key potential source locations in the lower(200 m)and middle(500 m)atmosphere(WPSCF>0.6).The WPSCF valuewas high at the 1000maltitude whichwas closer to the YMKsite than the near ground,indicating that the pollution transport capability in the upper atmosphere was limited.

关键词： Multi-axial differential optical absorption spectroscopy (MAX-DOAS) Nitrogen dioxide(NO2) Formaldehyde(HCHO) Potential source contribution function(PSCF)

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钾氨电子化合物中的准二维自旋-派尔斯相变

Science Bulletin 2024年第8期69卷 1027-1036页

作者：丁驰鲁清郭照芃黄天衡王俊杰韩瑜邢定钰孙建 National Laboratory of Solid State Microstructures School of Physics and Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China

Electron-phonon interactions and electron-electron correlations represent two crucial facets of condensed matter physics.For instance,in a half-filled spin-1/2 anti-ferromagnetic chain,the lattice dimerization induced by electron-nucleus interaction can be intensified by onsite Coulomb repulsion,resulting in a spin-Peierls state.Through first-principles calculations and crystal structure prediction methods,we have identified that under mild pressures,potassium and ammonia can form stable compounds:R3m K(NH_(3))_(2),Pm3 m K(NH_(3))_(2),and Cm K_(2)(NH_(3))_(3).Our predictions suggest that the R3 m K(NH_(3))_(2)exhibits electride characteristics,marked by the formation of interstitial anionic electrons(IAEs)in the interlayer space.These IAEs are arranged in quasi-two-dimensional triangular arrays.With increasing pressure,the electronic van-Hove singularity shifts toward the Fermi level,resulting in an augmented density of states and the onset of both Peierls and magnetic instabilities.Analyzing these instabilities,we determine that the ground state of the R3 m K(NH_(3))_(2)is the dimerized P2_(1)/m phase with zigzag-type anti-ferromagnetic IAEs.This state can be described by the triangular-lattice antiferromagnetic Heisenberg model with modulated magnetic interactions.Furthermore,we unveil the coexistence and positive interplay between magnetic and Peierls instability,constituting a scenario of spin-Peierls instability unprecedented in realistic 2D materials,particularly involving IAEs.This work provides valuable insights into the coupling of IAEs with the adjacent lattice and their spin correlations in quantum materials.

关键词： Quasi-two-dimensional Interstitial anionic electrons Potassium ammonia compounds Spin-Peierls transition Antiferromagnetism

Intelligent nanomaterials for cancer therapy:recent progresses and future possibilities

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Medical Review

Medical Review 2023年第4期3卷 321-342页

作者： Jing Wang Yuliang Zhao Guangjun Nie CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center of Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina center of Materials Science and optoelectronics Engineering University of Chinese Academy of SciencesBeijingChina CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center of Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China GBA research Innovation Institute for Nanotechnology Guangzhou 510700Guangdong ProvinceChina center of Materials Science and optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China

Intelligent nanomedicine is currently one of the most active frontiers in cancer therapy development.Empowered by the recent progresses of nanobiotechnology,a new generation of multifunctional nanotherapeutics and imaging platforms has remarkably improved our capability to cope with the highly heterogeneous and complicated na-ture of cancer.With rationally designed multifunctionality and programmable assembly of functional subunits,the in vivo behaviors of intelligent nanosystems have become increasingly tunable,making them more efficient in performing sophisticated actions in physiological and path-ological microenvironments.In recent years,intelligent nanomaterial-based theranostic platforms have showed great potential in tumor-targeted delivery,biological barrier circumvention,multi-responsive tumor sensing and drug release,as well as convergence with precise medication approaches such as personalized tumor vaccines.On the other hand,the increasing system complexity of anti-cancer nanomedicines also pose signiﬁcant challenges in charac-terization,monitoring and clinical use,requesting a more comprehensive and dynamic understanding of nano-bio interactions.This review aims to brieﬂy summarize the recent progresses achieved by intelligent nanomaterials in tumor-targeted drug delivery,tumor immunotherapy and temporospatially speciﬁc tumor imaging,as well as impor-tant advances of our knowledge on their interaction with biological systems.In the perspective of clinical translation,we have further discussed the major possibilities provided by disease-oriented development of anti-cancer nano-materials,highlighting the critical importance clinically-oriented system design.

关键词： intelligent nanomedicine anti-cancer nano-materials tumor microenvironment tumor vaccines immunotherapy personalized medication

Robust beam splitter with fast quantum state transfer through a topological interface

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Frontiers of physics 2023年第5期18卷 293-309页

作者： Jia-Ning Zhang Jin-Xuan Han Jin-Lei Wu Jie Song Yong-Yuan Jiang Department of optoelectronics Science Harbin Institute of TechnologyWeihai 264209China School of Physics Harbin Institute of TechnologyHarbin 150001China School of Physics and Microelectronics Zhengzhou UniversityZhengzhou 450001China Collaborative Innovation center of Extreme optics Shanxi UniversityTaiyuan 030006China Key Laboratory of Micro-Nano Optoelectronic Information System Ministry of Industry and Information TechnologyHarbin 150001China Key Laboratory of Micro-optics and Photonic Technology of Heilongjiang Province Harbin Institute of TechnologyHarbin 150001China

The Su–Schrieffer–Heeger(SSH)model,commonly used for robust state transfers through topologically protected edge pumping,has been generalized and exploited to engineer diverse functional quantum devices.Here,we propose to realize a fast topological beam splitter based on a generalized SSH model by accelerating the quantum state transfer(QST)process essentially limited by adiabatic requirements.The scheme involves delicate orchestration of the instantaneous energy spectrum through exponential modulation of nearest neighbor coupling strengths and onsite energies,yielding a significantly accelerated beam splitting process.Due to properties of topological pumping and accelerated QST,the beam splitter exhibits strong robustness against parameter disorders and losses of system.In addition,the model demonstrates good scalability and can be extended to two-dimensional crossed-chain structures to realize a topological router with variable numbers of output ports.Our work provides practical prospects for fast and robust topological QST in feasible quantum devices in large-scale quantum information processing.

关键词： quantum state transfer beam splitter topological router

RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3-and FADD-mediated cell death

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Cellular & Molecular Immunology 2024年第1期21卷 80-90页

作者： Xiaoxue Deng Lingxia Wang Yunze Zhai Qiuyue Liu Fengxue Du Yu Zhang Wenxing Zhao Tingtao Wu Yiwen Tao Jie Deng Yongbing Cao Pei Hao Jiazi Ren Yunli Shen Zuoren Yu Yuejuan Zheng Haibing Zhang Haikun Wang State Key Laboratory of Cardiology Shanghai East HospitalTongji University School of MedicineShanghai200120China CAS Key Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and InfectionChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai200031China CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200031China The research center for Traditional Chinese Medicine Shanghai Institute of Infectious Diseases and BiosecurityShanghai University of Traditional Chinese MedicineShanghai201203China Institute of Vascular Disease Shanghai TCM-Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai200433China

Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological conditions.However,the mechanisms underlying T_(reg)homeostasis remain incompletely understood.Here,we report that RIPK1 is crucial for T_(reg) cell survival and homeostasis.We generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death.Unlike conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis.However,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways.Thus,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.

关键词： Treg cell Homeostasis Apoptosis Necroptosis

Establishment of a humanized ST6GAL1 mouse model for influenza research

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Animal Models and Experimental Medicine 2024年第3期7卷 337-346页

作者： Lyu Chao Han Feng Gao Qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina NHC Key Laboratory of Biosafety National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

关键词： hST6GAL1 humanized mice influenza animal model

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

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Neural Regeneration research 2024年第10期19卷 2157-2174页

作者： Shihong Zhu Xiaoyin Liu Xiyue Lu Qiang Liao Huiyang Luo Yuan Tian Xu Cheng Yaxin Jiang Guangdi Liu Jing Chen Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina National Engineering research center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Pharmacy West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Out-patient Department West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Respiratory and Critical Care Medicine West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the

关键词： bioactive materials biomaterials exosomes neural regeneration scaffolds stem cells tissue engineering traumatic brain injury

Mitochondrial targeting sequence of magnetoreceptor MagR:More than just targeting

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Zoological research 2024年第3期45卷 468-477页

作者： Yanqi Zhang Peng Zhang Junjun Wang Jing Zhang Tianyang Tong Xiujuan Zhou Yajie Zhou Mengke Wei Chuanlin Feng Jinqian Li Xin Zhang Can Xie Tiantian Cai High Magnetic Field Laboratory Hefei Institutes of Physical ScienceChinese Academy of SciencesHefeiAnhui 230031China University of Science and Technology of China HefeiAnhui 230026China Department of Anatomy School of Basic MedicineAnhui Medical UniversityHefeiAnhui 230032China Institutes of Physical Science and Information Technology Anhui UniversityHefeiAnhui 230039China Key Laboratory of Tropical Translational Medicine of Ministry of Education NHC Key Laboratory of Tropical Disease ControlSchool of Tropical Medicine and The Second Affiliated HospitalHainan Medical UniversityHaikouHainan 571199China International Magnetobiology Frontier research center Science IslandHefeiAnhui 230031China Institute of Quantum Sensing Zhejiang UniversityHangzhouZhejiang 310027China

Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

关键词： Magnetoreceptor(MagR) N-terminal sequence Mitochondrial targeting signal Iron-sulfur cluster

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