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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

Neural Regeneration research 2024年第6期19卷 1206-1211页

作者： Matihias T.Wyss Christine Heuer Marina Herwerth Institute of Pharmacology and Toxicology University of Zurich Neuroscience Center zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders P2 receptor inhibitors purinergic system suramin

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PBX/Knotted 1 homeobox-2(PKNOX2)is a novel regulator of myocardial fibrosis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2231-2249页

作者： Liang Chen Haotong Li Xiaorui Liu Ningning Zhang Kui Wang Anteng Shi Hang Gao Deniz Akdis Ardan MSaguner Xinjie Xu Elena Osto Willem Van de Veen Guangyu Li Antoni Bayés-Genís Firat Duru Jiangping Song Xiangjie Li Shengshou Hu State Key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China School of Statistics and Data Science Nankai UniversityTianjinChina Department of Cardiology University Heart CenterUniversity Hospital Zurich and University of ZurichZurichSwitzerland Institute for Clinical Chemistry University Hospital Zurich and University of ZürichZurichSwitzerland Swiss Institute of Allergy and Asthma research(SIAF) University of ZurichDavosSwitzerland Heart Institute Hospital Universitari Germans Trias i PujolBadalonaCIBERCVSpain

Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing.However,the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors.In this study,we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors.With this unbiased protocol,we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes.Particularly in fibroblasts,a novel regulator,PKNOX2,was identified as being associated with physiological fibroblast activation in healthy hearts.To validate the roles of these transcription factors in maintaining homeostasis,we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling.The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation.Both gain-and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling.Moreover,fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis,respectively.In summary,this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle.With this optimized protocol,we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.

关键词： NOX2 homeostasis fibrosis

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Femoral Access with Ultrasound-Guided Puncture and Z-Stitch Hemostasis for Adults with Congenital Heart Diseases Undergoing Electrophysiological Procedures

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Congenital Heart Disease 2024年第1期19卷 85-92页

作者： Fu Guan Matthias Gass Florian Berger Heiko Schneider Firat Duru Thomas Wolber Arrhythmia and Electrophysiology Division Department of CardiologyUniversity Heart Center ZurichZurichSwitzerland Children’s research Center Zurich University Children’s HospitalZurichSwitzerland Center for Integrative Human Physiology University of ZurichZurichSwitzerland

Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efﬁcacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousﬁstula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.

关键词： Congenital heart disease cardiac electrophysiology cardiac catheterization femoral access hemostasis

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Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications

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Nano-Micro Letters 2024年第3期16卷 1-35页

作者： Sourav Dutta Seungmin Noh Roger Sanchis Gual Xiangzhong Chen Salvador Pané Bradley J.Nelson Hongsoo Choi Department of Robotics and Mechatronics Engineering Daegu Gyeongbuk Institute of Science and Technology(DGIST)Daegu 42988Republic of Korea DGIST‑ETH Microrobotics research Center DGISTDaegu 42988Republic of Korea Multi‑Scale Robotics Lab Institute of Robotics and Intelligent SystemsETH Zurich8092 ZurichSwitzerland Institute of Optoelectronics State Key Laboratory of Photovoltaic Science and TechnologyShanghai Frontiers Science Research Base of Intelligent Optoelectronics and PerceptionFudan UniversityShanghai 200433People’s Republic of China

Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation.Metal-based degradable micromotor composed of magnesium(Mg),zinc(Zn),and iron(Fe)have promise due to their nontoxic fuel-free propulsion,favorable biocompatibility,and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media,efficient cargo delivery and favorable biocompatibility.A noteworthy number of degradable metal-based micromotors employ bubble propulsion,utilizing water as fuel to generate hydrogen bubbles.This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications.In addition,understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance.Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor.Here we review the design and recent advancements of metallic degradable micromotors.Furthermore,we describe the controlled degradation,efficient in vivo drug delivery,and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications.Moreover,we discuss micromotors’efficacy in detecting and destroying environmental pollutants.Finally,we address the limitations and future research directions of degradable metallic micromotors.

关键词： Magnesium Zinc Iron Biodegradable microrobot Biomedical Environmental

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Recovery and in-situ reduction of precious metals by graphdiyne and graphdiyne oxide for antibacterial use

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Rare Metals 2024年第4期43卷 1747-1757页

作者： Ming-Ji Jiang Ya-Na Zhang Ling-Shen Meng Jing Kang Yong-Jun Li Alideertu Dong College of Chemistry and Chemical Engineering Inner Mongolia University Engineering research Center of Dairy Quality and Safety Control Technology Ministry of EducationInner Mongolia University Department of Chemistry University of Zurich laboratory of Organic Solids and Beijing National laboratory for Molecular Sciences Institute of ChemistryChinese Academy of Sciences

Based on the in-situ self-reduction and chemical stability,graphdiyne（GDY） and graphdiyne oxide（GDYO） are used as trapping agents to investigate the ability for recovering Au3+,Ag+,and Pd2+under different pH values and interfering ions.Under strong acidity at pH=1,these two agents demonstrate high select recovery towards the three precious metal ions,which could be insitu reduced to nanoparticles（NPs）.In addition,superparamagnetic Fe3O4NPs are deposited on the surfaces of GDY and GDYO.The magnetic responses enable GDYFe3O4to recover precious metals conveniently and efficiently by the aid of an external magnetic field.This study also confirms the antibacterial activity of the as-recovered NPs deposited on GDY and GDYO against Escherichia coli and Staphylococcus aureus(1 × 10～5 colony-forming unit（CFU）·ml-1),and the antibacterial rates are 100%.This strategy of recovering precious metals and subsequently reusing to combat pathogens will be of great significance for environmental remediation and biomedical applications.

关键词： Graphdiyne In-situ reduction Recovery Precious metals Antibacterial

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Harnessing the power of pericytes and hypoxia-inducible factor-1 to modulate stroke outcome

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Neural Regeneration research 2024年第3期19卷 473-474页

作者： Omolara O.Ogunshola Chih-Chieh Tsao Institute of Veterinary Physiology Vetsuisse FacultyUniversity of ZurichZurichSwitzerland

The human brain has exceedingly high metabolic demands.The cerebral vasculature has the critical task of providing sufficient blood supply to meet this demand.The sudden interruption of blood flow to the brain,as observed during ischemic stroke,results in acute neurological injury with devastating consequences-a high rate of adult disability and death.Ischemic stroke is thus a vascular disorder with a dramatic neurological impact.There is an urgent need for more effective disease management to combat stroke as current treatment paradigms,focusing on vascular recanalization and neuroprotection,have only limited clinical success.Since accumulating data suggests successful long-term neuroprotection is unlikely to be achievable without a functional microvascular network,strategies that reduce endothelial dysfunction could be indispensable.Encouragingly,very recent evidence highlighted herein suggests protecting the humble pericyte may be a new approach to reaching this goal.

关键词： consequences exceeding herein

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Energy Management of Price-maker Community Energy Storage by Stochastic Dynamic Programming

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 492-503页

作者： Lirong Deng Xuan Zhang Tianshu Yang Hongbin Sun Yang Fu Qinglai Guo Shmuel S.Oren Department of Electrical Engineering Shanghai University of Electric PowerShanghai 200000China Tsinghua-Berkeley Shenzhen Institute Tsinghua UniversityShenzhen 518055China Department of Industrial Engineering and Operations research University of California BerkeleyBerkeleyCAUSA Risk Analytics and Optimization Chair EPFLSwitzerlandand also with Power Systems LaboratoryETH Zurich8092 ZurichSwitzerland State Key laboratory of Power Systems Department of Electrical EngineeringTsinghua UniversityBeijing 100084China

In this paper,we propose an analytical stochastic dynamic programming(SDP)algorithm to address the optimal management problem of price-maker community energy storage.As a price-maker,energy storage smooths price differences,thus decreasing energy arbitrage value.However,this price-smoothing effect can result in significant external welfare changes by reduc-ing consumer costs and producer revenues,which is not negligible for the community with energy storage systems.As such,we formulate community storage management as an SDP that aims to maximize both energy arbitrage and community welfare.To incorporate market interaction into the SDP format,we propose a framework that derives partial but sufficient market information to approximate impact of storage operations on market prices.Then we present an analytical SDP algorithm that does not require state discretization.Apart from computational efficiency,another advantage of the analytical algorithm is to guide energy storage to charge/discharge by directly comparing its current marginal value with expected future marginal value.Case studies indicate community-owned energy storage that maximizes both arbitrage and welfare value gains more benefits than storage that maximizes only arbitrage.The proposed algorithm ensures optimality and largely reduces the computational complexity of the standard SDP.Index Terms-Analytical stochastic dynamic programming,energy management,energy storage,price-maker,social welfare.

关键词： Analytical stochastic dynamic programming energy management energy storage price-maker social welfare

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Advances in non-invasive imaging of proteinopathies in animal models of neurodegenerative diseases

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Neural Regeneration research 2024年第10期19卷 2115-2116页

作者： Lei Cao Bin Ji Ruiqing Ni Changes Technology Corporation Ltd. ShanghaiChina Fudan University ShanghaiChina School of Pharmacy Fudan UniversityShanghaiChina Institute for Biomedical Engineering University of Zurich&ETH Zurich Institute for Regenerative MedicineUniversity of ZurichZurichSwitzerland

Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.

关键词： diseases degenerative clinical

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Challenging the term symbiosis in plant-microbe associations to create an understanding across sciences

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Journal of Integrative Plant Biology 2024年第1期66卷 7-11页

作者： Anna Neubauer Daniela Aros‐Mualin Vicente Mariscal Péter Szövényi Department of Systematic and Evolutionary Botany University of ZurichZurich 8008Switzerland zurich‐Basel Plant Science Center Zurich 8092Switzerland Instituto de Bioquímica Vegetal y Fotosíntesis CSIC y Universidad de SevillaSevilla 41092Spain

THE IMPORTANCE OF WELL DEFINED TERMINOLOGY,Effective communication across fields and disciplines relies on well defined terminology.Standardized use of accurate definitions has been advocated by scientists across vari... 详细信息

关键词： terminology definition fields

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