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Cellular & molecular Immunology 2020年第2期17卷 123-132页

作者： Yifan Zhan Nancy Wang Ajithkumar Vasanthakumar Yuxia Zhang michael Chopin Stephen L.Nutt Axel Kallies andrew m.lew The Walter&Eliza Hall Institute of medical Research ParkvilleVIC 3052Australia Department of medical Biology University of MelbourneParkvilleVIC 3010Australia Guangzhou Institute of Paediatrics Guangzhou Women and Children’s Medical CentreGuangzhou Medical University510623 GuangzhouGuangdongChina Department of microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneParkvilleVIC 3010Australia

A wide array of chemokine receptors,including CCR2,are known to control Treg ***,we report that CCR2 regulates Tregs beyond *** found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg *** a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type(WT)and CCR2−/−***,CCR2 deficiency resulted in profound loss of CD25 ^(hi) FoxP3^(+) Tregs in secondary lymphoid organs as well as in peripheral ***2−/−Treg cells were also functionally inferior to WT ***,these changes to Treg cells did not depend on CCR2+monocytes/moDCs(the cells where CCR2 receptors are most abundant).Rather,we demonstrated that CCR2 was required for TLR-stimulated,but not TCR-or IL-2-stimulated,CD25 upregulation on Treg ***,we propose that CCR2 signaling can increase the fitness of FoxP3^(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.

关键词： CCR2 CD25 organs

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1205-1215页

作者： Xiaoyan Liu Zhe Li Shuai Liu Jing Sun Zhanghua Chen min Jiang Qingling Zhang Yinghua Wei Xin Wang Yi-You Huang Yinyi Shi Yanhui Xu Huifang Xian Fan Bai Changxing Ou Bei Xiong andrew m.lew Jun Cui Rongli Fang Hui Huang Jincun Zhao Xuechuan Hong Yuxia Zhang Fuling Zhou Hai-Bin Luo Department of Hematology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Dawu County People’s Hospital Xiaogan 432826China State Key Laboratory of Respiratory Diseases National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Guangzhou Institute of Pediatrics Guangzhou Women and Children’s Medical CenterState Key Laboratory of Respiratory DiseasesGuangzhou Medical UniversityGuangzhou 510623China Biomedical Pioneering Innovation Center(BIOPIC) School of Life SciencesPeking UniversityBeijing 100871China Department of Infectious Disease and Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Center for Innovative marine Drug Screening&Evaluation(QNLm) School of Medicine and PharmacyOcean University of ChinaQingdao 266100China Walter and Eliza Hall Institute of medical Research and Department of microbiology&Immunology University of MelbourneParkvilleVic 3052Australia School of Life Sciences Sun Yat-sen UniversityGuangzhou 510006China Cardiovascular Department The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China State Key Laboratory of Virology College of ScienceInnovation Center for Traditional Tibetan Medicine Modernization and Quality ControlMedical CollegeTibet UniversityLhasa 850000China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery(mOE) Hubei Province Engineering and Technology Research Center for Fluorinated PharmaceuticalsWuhan University School of Pharmaceutical SciencesWuhan 430071China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan *** antivirals with safe clinical profile are urgently needed to improve the overall *** an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease *** virtual screening of a *** approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in *** a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(Pmphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control *** particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.

关键词： Dipyridamole SARS-CoV-2 COVID-19 Treatment D-dimer Severe cases

CIS controls the functional polarization of Gm-CSF-derived macrophages

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Cellular & molecular Immunology 2023年第1期20卷 65-79页

作者： Shengbo Zhang Jai Rautela Naiara G.Bediaga Tatiana B.Kolesnik Yue You Junli Nie Laura F.Dagley Justin Bedo Hanqing Wang Li Sun Robyn Sutherland Elliot Surgenor Nadia Iannarella Rhys Allan Fernando Souza-Fonseca-Guimaraes Yi Xie Qike Wang Yuxia Zhang Yuekang Xu Stephen L.Nutt andrew m.lew Nicholas D.Huntington Sandra E.Nicholson michaël Chopin Yifan Zhan Walter and Eliza Hall Institute of medical Research ParkvilleVICAustralia Department of medical Biology University of MelbourneParkvilleVICAustralia Department of Biochemistry and molecular Biology Biomedicine Discovery InstituteMonash UniversityClaytonVICAustralia oNKo-Innate Pty Ltd Moonee PondsVICAustralia Department of Computing and Information Systems University of MelbourneParkvilleVICAustralia Department of Respiratory medicine Guangzhou Institute of PediatricsGuangzhou Women and Children’s Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical UniversityGuangzhouGuangdongChina College of Biological Science Anhui Normal UniversityHefeiChina University of Queensland Diamantina Institute University of QueenslandTranslational Research InstituteBrisbaneQLDAustralia Program in Cardiovascular and metabolic Disorders Duke-NUS Medical SchoolDukeSingapore Drug Discovery Shanghai Huaota BiopharmShanghaiChina

The cytokine granulocyte-macrophage-colony stimulating factor (Gm-CSF) possesses the capacity to differentiate monocytes into macrophages (mØs) with opposing functions, namely, proinflammatory m1-like mØs and immunosuppressive m2-like mØs. Despite the importance of these opposing biological outcomes, the intrinsic mechanism that regulates the functional polarization of mØs under Gm-CSF signaling remains elusive. Here, we showed that Gm-CSF-induced mØ polarization resulted in the expression of cytokine-inducible SH2-containing protein (CIS) and that CIS deficiency skewed the differentiation of monocytes toward immunosuppressive m2-like mØs. CIS deficiency resulted in hyperactivation of the JAK-STAT5 signaling pathway, consequently promoting downregulation of the transcription factor Interferon Regulatory Factor 8 (IRF8). Loss- and gain-of-function approaches highlighted IRF8 as a critical regulator of the m1-like polarization program. In vivo, CIS deficiency induced the differentiation of m2-like macrophages, which promoted strong Th2 immune responses characterized by the development of severe experimental asthma. Collectively, our results reveal a CIS-modulated mechanism that clarifies the opposing actions of Gm-CSF in mØ differentiation and uncovers the role of Gm-CSF in controlling allergic inflammation.

关键词： CIS Gm-CSF macrophage m2 m1

Designing architected materials for mechanical compression via simulation, deep learning, and experimentation

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npj Computational materials 2023年第1期9卷 1534-1542页

作者： andrew J.lew Kai Jin markus J.Buehler Laboratory for Atomistic and molecular mechanics(LAmm) Massachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA 02139USA Department of Chemistry Massachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA 02139USA Center for Computational Science and Engineering Schwarzman College of ComputingMassachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA 02139USA

Architected materials can achieve enhanced properties compared to their plain *** architecting serves as a powerful design lever to achieve targeted behavior without changing the base ***,the connection between architected structure and resultant properties remains an open field of great interest to many fields,from aerospace to civil to automotive ***,we focus on properties related to mechanical compression,and design hierarchical honeycomb structures to meet specific values of stiffness and compressive *** do so,we employ a combination of techniques in a singular workflow,starting with molecular dynamics simulation of the forward design problem,augmenting with data-driven artificial intelligence models to address the inverse design problem,and verifying the behavior of de novo structures with experimentation of additively manufactured *** thereby demonstrate an approach for architected design that is generalizable to multiple material properties and agnostic to the identity of the base material.

关键词： thereby additive starting

A Dynamic Organic Structuring-Directing Agent for Pure-Silica-Zeolite AST and LTA Syntheses

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催化学报 2012年第1期33卷 85-91页

作者： minwei SUN Heather K.HUNT Christopher m.lew Rui CAI Yan LIU Yushan YAN Department of Chemical and Environmental Engineering University of CaliforniaRiversideCalifornia 92521USA Chemical Engineering California Institute of TechnologyPasadenaCalifornia 91125USA

Pure-silica-zeolite (PSZ ) 著名计算机生产厂商和 LTA 被使用一样的指导结构的代理人(SDA ) 成功地综合分子，但是在不同集中。动态器官的 SDA 被建议讨论在著名计算机生产厂商和 LTA 之间的阶段辨别的机制。数据建议进在不同集中由... 详细信息

Pure-silica-zeolite (PSZ ) 著名计算机生产厂商和 LTA 被使用一样的指导结构的代理人(SDA ) 成功地综合分子，但是在不同集中。动态器官的 SDA 被建议讨论在著名计算机生产厂商和 LTA 之间的阶段辨别的机制。数据建议进在不同集中由的更暗淡或更整齐的建筑群自我装配的 SDA 分子罐头 - 相互作用，和这些差别能被利用有选择地综合 PSZ 著名计算机生产厂商或 LTA。从 Liebau 的规则的这些偏差显示在在溶液的 SDA 化学，结构，和顺序的小面值硬币能在沸石合成的结构选择上有大影响。

关键词： zeolite synthesis dynamic structure-directing agent π-π conjugation Liebau's rules

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： moawiah m.Naffaa Department of Psychology and Neuroscience Duke UniversityDurhamNCUSA Department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： Josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

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Neural Regeneration Research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya Kira m.Holmström Henri J.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

Search for microglia-specific peptides:advances in the discovery toolbox

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Neural Regeneration Research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle m.Koss Department of Surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;m1 and m2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

SBL-JP-0004: A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

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Oncology research 2025年第1期33卷 235-243页

作者： Hassan m Otifi Department of Pathology College of Medicine King Khalid University Abha 62521 Saudi Arabia.

Background:Gastric cancer (GC) remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and PI3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in GC progression, making them attractive targets for therapeutic interventions.methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases. KATOIII and SNU-5 GC cells were used for evaluation.Results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases, as evidenced by molecular docking scores and molecular dynamics simulations. Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins. SBL-JP-0004 displayed an half-maximal inhibitory concentration (IC) value of 118.9 nm against JAK2 kinase and 200.9 nm against PI3KCD enzymes. SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells, with half-maximal growth inhibitory concentration (GI) values of 250.8 and 516.3 nm, respectively. A significant elevation in the early phase apoptosis (28.53% in KATOIII cells and 26.85% in SNU-5 cells) and late phase apoptosis (17.37% in KATOIII cells and 10.05% in SNU-5 cells) were observed with SBL-JP-0004 treatment compared to 2.1% and 2.83% in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Dual inhibition Gastric cancer (GC) JAK2 molecular docking molecular dynamics simulation PI3KCD SBL-JP-0004