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DDAH1 promotes neurogenesis and neural repair in cerebral ischemia

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2097-2118页

作者： Qiming Gao Pinfei Ni Yilin Wang Peiyun Huo Xiaojie Zhang Sihan Wang Fuyao Xiao Yixuan Li Wei Feng Juntao Yuan Teng Zhang Qiang Li Boyu Fan Yuhao Kan Zhirui Li Yimiao Qi Junfei Xing Zhenghong Yang Haixiao Cheng Xinran Gao Xiaoyan Feng Ming Xue Yang Liu Yumin Luo Zhongbing Lu Yuming Zhao department of Pharmacology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Cerebrovascular Diseases Research Institute and department of Neurology Xuanwu Hospital of Capital Medical UniversityBeijing 100053China State Key laboratory for Structural Chemistry of Unstable and Stable Species Institute of ChemistryChinese Academy of SciencesBeijing 100190China College of Life Science University of Chinese Academy of SciencesBeijing 100049China department of laboratory Animal School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China department of physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Choline acetyltransferase(ChAT)-positive neurons in neural stem cell(NSC)niches can evoke adult neurogenesis(AN)and restore impaired brain function after injury,such as acute ischemic stroke(AIS).However,the relevant mechanism by which ChAT+neurons develop in NSC niches is poorly understood.Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1(DDAH1),a hydrolase for asymmetric NG,NG-dimethylarginine(ADMA),regulated genes responsible for the synthesis and transportation of acetylcholine(ACh)(Chat,Slc5a7 and Slc18a3)after stroke insult.The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT,possibly through hypoxia-inducible factor 1α(HIF-1α).KC7F2,an inhibitor of HIF-1α,abolished DDAH1-induced ChAT expression and suppressed neurogenesis.As expected,DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity.By comparing the results among Ddah1 general knockout(KO)mice,transgenic(TG)mice and wild-type(WT)mice,we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone(SGZ)under ischemic insult.As a result,DDAH1 may promote cognitive and motor function recovery against stroke impairment,while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

关键词： DDAH1 Neurogenesis Neural repair ChAT HIF-1α ACh Stroke ADMA

Comprehensive and personalized approach is a critical area for developing remote cardiac rehabilitation programs

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World Journal of Clinical Cases 2024年第12期12卷 2009-2015页

作者： Garyfallia Pepera Varsamo Antoniou Jing Jing Su Rose Lin Ladislav Batalik Clinical Exercise physiology and Rehabilitation Research laboratory Department of PhysiotherapyFaculty of Health SciencesUniversity of ThessalyLamia GR35100Greece School of Nursing The Hong Kong Polytechnic UniversityHong Kong 999077China University of Rochester School of Nursing New YorkNY 14602United States department of Rehabilitation University Hospital BrnoBrno 62500Czech Republic department of Public Health Faculty of MedicineMasaryk UniversityBrno 62500Czech Republic

In the evolving landscape of cardiac rehabilitation(CR),adopting digital technologies,including synchronous/real-time digital interventions and smart applications,has emerged as a transformative approach.These technologies offer realtime health data access,continuous vital sign monitoring,and personalized educational enhanced patient self-management and engagement.Despite their potential benefits,challenges and limitations exist,necessitating careful consideration.Synchronous/real-time digital CR involves remote,two-way audiovisual communication,addressing issues of accessibility and promoting home-based interventions.Smart applications extend beyond traditional healthcare,providing real-time health data and fostering patient empowerment.Wearable devices and mobile apps enable continuous monitoring,tracking of rehabilitation outcomes,and facilitate lifestyle modifications crucial for cardiac health maintenance.As digital CR progresses,ensuring patient access,equitable implementation,and addressing the digital divide becomes paramount.Artificial intelligence holds promise in the early detection of cardiac events and tailoring patient-specific CR programs.However,challenges such as digital literacy,data privacy,and security must be addressed to ensure inclusive implementation.Moreover,the shift toward digital CR raises concerns about cost,safety,and potential depersonalization of therapeutic relationships.A transformative shift towards technologically enabled CR necessitates further research,focusing not only on technological advancements but also on customization to meet diverse patient needs.Overcoming challenges related to cost,safety,data security,and potential depersonalization is crucial for the widespread adoption of digital CR.Future studies should explore integrating moral values into digital therapeutic relationships and ensure that digital CR is accessible,equitable,and seamlessly integrated into routine cardiac care.Theoretical frameworks that accommodate the dynamic quality of real-time monitoring and

关键词： Cardiac rehabilitation Digital approaches Remote care Equity in technology access Synchronous/real-time interventions Digital innovation in healthcare

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of Neurology of the Second Afliated Hospital and department of Human Anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of Human Reproduction and Developmental Genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral Sclerosis.In a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into fibrils.Cellular and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent years.This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and secretion.Debates on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also discussed.Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

The underlying mechanism of variety–water–nitrogen–stubble damage interactions on yield formation in ratoon rice with low stubble height under mechanized harvesting

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Journal of Integrative Agriculture 2024年第3期23卷 806-823页

作者： Jingnan Zou Ziqin Pang Zhou Li Chunlin Guo Hongmei Lin Zheng Li Hongfei Chen Jinwen Huang Ting Chen Hailong Xu Bin Qin Puleng Letuma Weiwei Lin Wenxiong Lin College of Life Sciences Fujian Agriculture and Forestry University(FAFU)/Fujian Key Laboratory for Agroecological Processes and Safety MonitoringFuzhou 350002China College of Agriculture FAFU/Fujian Key Laboratory for Crop Physiology and Molecular EcologyFuzhou 350002China Institute of Oceanography College of Geography and OceanographyMinjiang UniversityFuzhou 350108China Crop Science department The National University of LesothoRoma 00100Lesotho The Agricultural Extension Station of Pucheng County Nanping 353400China

Agronomic measures are the key to promote the sustainable development of ratoon rice by reducing the damage from mechanical crushing to the residual stubble of the main crop, thereby mitigating the impact on axillary bud sprouting and yield formation in ratoon rice. This study used widely recommended conventional rice Jiafuzhan and hybrid rice Yongyou 2640 as the test materials to conduct a four-factor block design field experiment in a greenhouse of the experimental farm of Fujian Agricultural and Forestry University, China from 2018 to 2019.The treatments included fertilization and no fertilization, alternate wetting and drying irrigation and continuous water flooding irrigation, and plots with and without artificial crushing damage on the rice stubble. At the same time, a 13C stable isotope in-situ detection technology was used to fertilize the pot experiment. The results showed significant interactions among varieties, water management, nitrogen application and stubble status.Relative to the long-term water flooding treatment, the treatment with sequential application of nitrogen fertilizer coupled with moderate field drought for root-vigor and tiller promotion before and after harvesting of the main crop, significantly improved the effective tillers from low position nodes. This in turn increased the effective panicles per plant and grains per panicle by reducing the influence of artificial crushing damage on rice stubble and achieving a high yield of the regenerated rice. Furthermore, the partitioning of 13C assimilates to the residual stubble and its axillary buds were significantly improved at the mature stage of the main crop, while the translocation rate to roots and rhizosphere soil was reduced at the later growth stage of ratooning season rice. This was triggered by the metabolism of hormones and polyamines at the stem base regulated by the interaction of water and fertilizer at this time. We therefore suggest that to achieve a high yield of ratoon rice with low stubble height under mechanized harvest

关键词： mechanized harvesting ratoon rice rice stubble yield attributes

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim Böttrich Pascal Bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer Robert Ringseis Klaus Eder Karsten Krüger Christopher Weyh department of Exercise physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition physiology Justus-Liebig-University GiessenGiessen 35390Germany

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang department of physiology School of Medicine Nantong University department of Neurosurgery Huashan Hospital Shanghai Medical College Fudan University National Center for Neurological Disorders Shanghai Key laboratory of Brain Function Restoration and Neural Regeneration State Key laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institute of Brain Science Fudan University

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neur

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Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

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Neural Regeneration Research 2024年第10期19卷 2189-2201页

作者： Jesus Amo-Aparicio Charles A.Dinarello Ruben Lopez-Vales department of Medicine University of ColoradoAuroraCOUSA Institute of Neurosciences and Department Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos ⅢSpain

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

关键词： central nervous system fatty acid oxidation glycolysis inflammation macrophage metabolism microglia neurodegeneration oxidative phosphorylation

Respiratory Flow Rates of Metal Welders Compared to a Population Not Exposed to Metal Welding Dust

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Open Journal of Respiratory Diseases 2024年第2期14卷 51-59页

作者： Robert Faomowe Foko Abdou Khadir Sow Awa Ba Mor Diaw Fatoumata Bah Mame Saloum Coly Absa Lam Cheikh Diop Aminata Toure Abdoulaye Ba Abdoulaye Samb Arame Mbengue Mathilde Cabral Mamadou Fall laboratory of Toxicology and Hydrology Faculty of Medicine Pharmacy and Odontostomatology Cheikh Anta Diop University of Dakar Dakar-Fann Senegal laboratory of physiology and Functional Exploration Faculty of Medicine Pharmacy and Odontostomatology Cheikh Anta Diop University of Dakar Dakar-Fann Senegal laboratory of physiology and Functional Exploration Alioune DIOP University of Bambey Bambey Senegal laboratory of physiology UFR of Health Sciences Functional Exploration Department Thies Regional Hospital Center Thies Senegal

Background: The welding trade includes many industrial activities in both the formal and informal sectors. Workers in this professional environment do not have access to individual and collective means of protection adapted to the activity, which exposes them to the dust emitted during their activity and therefore contributes to increasing the risk of developing respiratory disorders in this population. Objective: Our study aimed to evaluate the ventilatory function of metal welders in the city of Dakar. Method: This was a comparative study based on the analysis of the spirometric parameters of metal welders working in the city of Dakar (Senegal) with those of a control group of the same kind, selected from the general population. Measurements of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and maximum mid expiratory flow (MMEF) were measured. Results: A total of 75 men between the ages of 19 and 61 were recruited and divided into two groups (43 controls and 32 welders). The welding population had more frequent distal and central obstructions and pulmonary restriction compared to the control group. The metals most commonly used by welders were aluminum for welders who had an obstruction, while for those who had a restriction, iron was the most used metal. Signs of metal fever were frequently found in welders, especially those with ventilatory disorders. Conclusion: The prevalence of respiratory disorders observed is close to that observed in industrial environments, where exposure levels are the highest. The lack of personal protective equipment could also be a significant risk factor in the development of these disorders.

关键词： Welder Occupational Exposure Spirometric Disorder Metal Fever Dakar

Mitigating growth-stress tradeoffs via elevated TOR signaling in rice

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Molecular Plant 2024年第2期17卷 240-257页

作者： Wei Li Jiaqi Liu Zeqi Li Ruiqiang Ye Wenzhen Chen Yuqing Huang Yue Yuan Yi Zhang Huayi Hu Peng Zheng Zhongming Fang Zeng Tao Shiyong Song Ronghui Pan Jian Zhang Jumim Tu Jen Sheen Hao Du State Key laboratory of Rice Biology College of Agriculture and BiotechnologyZhejiang UniversityYu-Hang-Tang Road No.866Hangzhou 310058China ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 311215China Hainan Institute of Zhejiang University Sanya 572025China National Key laboratory of Plant Molecular Genetics CASCenter for Excellence in Molecular Plant SciencesShanghai lnstitute of Plant Physiology and EcologyChineseAcademy of SciencesShanghai 200032China Key laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region(Ministry of Education) College of Agricultural SciencesGuizhouUniversityGuiyang 550025China State Key laboratory of Rice Biology and Breeding China National Rice Research InstituteHangzhou 311400China department of Molecular Biology and Center for Computational and Integrative Biology Massachusetts General Hospitaland Department of GeneticsHarvard Medical SchoolBostonMA02114USA

Rice production accounts for approximately half of the freshwater resources utilized in agriculture,result-ing in greenhouse gas emissions such as methane(CH4)from flooded paddy fields.To address this chal-lenge,environmentally friendly and cost-effective water-saving techniques have become widely adopted in rice cultivation.However,the implementation of water-saving treatments(WsTs)in paddy-field rice has been associated with a substantial yield loss of up to 50%as well as a reduction in nitrogen use efficiency(NUE).In this study,we discovered that the target of rapamycin(TOR)signaling pathway is compromised in rice under WsT.Polysome profiling-coupled transcriptome sequencing(polysome-seq)analysis unveiled a substantial reduction in global translation in response to WST associated with the downregulation of TOR activity.Molecular,biochemical,and genetic analyses revealed new insights into the impact of the positive TOR-S6K-RPS6 and negative TOR-MAF1 modules on translation repression under WST.Intriguingly,ammonium exhibited a greater ability to alleviate growth constraints under WsT by enhancing TOR signaling,which simultaneously promoted uptake and utilization of ammonium and nitrogen allocation.We further demonstrated that TOR modulates the ammonium transporter AMT1;1 as well as the amino acid permease APP1 and dipeptide transporter NPF7.3 at the translational level through the 5'untranslated region.Collectively,these findings reveal that enhancing TOR signaling could mitigate rice yield penalty due to WST by regulating the processes involved in protein synthesis and NUE.Our study will contribute to the breeding of new rice varieties with increased water and fertilizer utilization efficiency.

关键词： target of rapamycin TOR water-saving rice low-carbon agriculture drought nitrogen use efficiency NUE