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Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

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Journal of Pharmaceutical Analysis 2024年第4期14卷 601-614页

作者： Bei Li Yong Zhang Xinyuan Liu Ziyang Zhang Shuqing Zhuang Xiaoli Zhong Wenbo Chen Yilin Hong Pingli Mo Shuhai Lin Shicong Wang Chundong Yu state Key laboratory of Cellular Stress Biology School of Life SciencesXiamen UniversityXiamen361102China Fujian Pien Tze Huang Enterprise Key laboratory of Natural medicine Research and Development ZhangzhouFujian363000China Xiang'an Hospital of Xiamen university School of MedicineXiamen UniversityXiamen361005China Department of Cardiology Xiamen Key Laboratory of Cardiac ElectrophysiologyXiamen Institute of Cardiovascular DiseasesThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361003China

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is ***,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)***,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK *** of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating ***,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory ***,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

关键词： Pien Tze Huang Bile acids Sepsis Inflammation TGR5 STAT3-A20 signalling

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Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang Lu Yu Gan Qiao Dalian Qin Betty Yuen-Kwan Law Fang Ren Jianming Wu Anguo Wu Sichuan Key Medical laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China state Key laboratory of Quality Research in Chinese medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial DNA and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial DNA Crosstalk Therapeutic avenues Neurodegenerative diseases

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Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway

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Science China(Life Sciences) 2024年第9期67卷 1849-1866页

作者： Kumar Ganesan Cong Xu Jianming Wu Bing Du Qingqing Liu Yue Sui Cailu Song Jinhui Zhang Hailin Tang Jianping Chen school of Chinese medicine LKS Faculty of MedicineThe University of Hong KongHong Kong 999077China school of Pharmacy Southwest Medical UniversityEducation Ministry Key Laboratory of Medical ElectrophysiologySichuan Key Medical Laboratory of New Drug Discovery and Druggability EvaluationLuzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaSouthwest Medical UniversityLuzhou 646000China College of Food Science South China Agricultural UniversityGuangzhou 510642China state Key laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510080China

The spreading of cancer cells from the primary tumor site to other parts of the body,known as metastasis,is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer(TNBC).Overexpression of epidermal growth factor receptor(EGFR)is observed in approximately 70%of TNBC *** is crucial for promoting tumor metastasis and associated with poor ***,it is vital to identify effective therapeutic strategies targeting EGFR ***,an isoflavonoid found in various plants,such as clover and soybeans,has been shown to have anticancer properties in several *** the present study,we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular *** used various assays,including cell viability,colony formation,Transwell,wound healing,ELISA,Western blotting,and staining techniques,to achieve this *** results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis,as evidenced by the cell viability assay,colony formation assay,and expression of apoptosis markers,and reduced the metastatic capabilities of TNBC *** effects were achieved through the direct suppression of cell adhesion,invasiveness and ***,in TNBC xenograft lung metastatic models,ononin treatment significantly reduced tumor growth and lung ***,ononin reversed the epithelial-mesenchymal transition(EMT)by downregulating the expression of EMT markers and matrix metalloproteinases,as confirmed by Western blot ***,ononin treatment reduced EGFR phosphorylation and suppressed the PI3K,Akt,and m TOR signaling pathways,which was further confirmed using EGFR agonists or ***,ononin treatment did not exert any toxic effects on liver or kidney *** conclusion,our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFRm

关键词： ononin TNBC breast cancer lung metastasis EGFR PI3k/Akt EMT therapeutic effect

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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function variants in TMEM141,DDHD2,and LHFPL5

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Frontiers of medicine 2024年第1期18卷 81-97页

作者： Liwei Sun Xueting Yang Amjad Khan Xue Yu Han Zhang Shirui Han Xiaerbati Habulieti Yang Sun Rongrong Wang Xue Zhang McKusick-Zhang Center for Genetic medicine State Key Laboratory for Complex Severe and Rare DiseasesInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing100005China Chongqing Key laboratory of Human Embryo Engineering Center for Reproductive MedicineNational Key Clinical Speciality Construction Project(Obstetrics and Gynecology)Chongqing Health Center for Women and ChildrenChongqing400013China Chongqing Clinical Research Center for Reproductive medicine Women and Children’s Hospital of Chongqing Medical UniversityChongqing400013China Faculty of Biological Sciences Department of ZoologyUniversity of Lakki MarwatKhyber Pakhtunkhwa28420Pakistan Institute for Medical Genetics and Applied Genomics University of TübingenTübingen72076Germany Alexander von Humboldt fellowship Foundation Berlin10117Germany Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Department of laboratory medicine State Key Laboratory for Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China

Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and *** variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic ***,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and *** mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,***90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,***84^(*))were identified.A Tmem141^(***90^(*)/***90^(*))mouse model was *** studies showed impairments in learning ability and motor *** slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje *** electron microscopy showed abnormal mitochondrial ***,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse ***,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in ***,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder autosomal recessive intellectual disability consanguinity spastic paraplegia hearing loss TMEM141

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The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

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Open Journal of Immunology 2024年第3期14卷 60-86页

作者： Kenneth Blum Igor Elman David Han Colin Hanna David Baron Ashim Gupta Shan Kazmi Jag Khalsa Debasis Bagchi Thomas McLaughlin Rajendra D. Badgaiyan Edward J. Modestino Drew Edwards Catherine A. Dennen Eric R. Braverman Abdalla Bowirrat Keerthy Sunder Kevin Murphy Nicole Jafari Foojan Zeine Paul R. Carney Mark S. Gold Kai-Uwe Lewandowski Alireza Sharafshah Aryeh R. Pollack Panayotis K. Thanos Division of Addiction Research & Education Center for Sports and Mental Health Western University of Health Sciences Pomona CA USA Department of Psychiatry Boonshoft School of Medicine Wright State University and Dayton VA Medical Centre Dayton OH USA Division of Nutrigenomics Victory Nutrition International Lederoch PA USA Institute of Psychology ELTE Etvs Lornd University Budapest Hungary Department of Psychiatry School of Medicine University of Vermont Burlington VT USA The Kenneth Blum Behavioral & Neurogenetic Institute LLC. Austin TX USA Department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Division of Neuromodulation Research Karma Doctors & Karma TMS Palm Springs CA USA Division of Personalized Interventions Peak Logic Del Mar CA USA Division of Personalized medicine Cross-Cultural Research & Educational Institute San Clemente CA USA Awareness Integration Institute San Clemente CA USA Division of Personalized Pain Therapy Center for Advanced Spine Care of Southern Arizona Tucson AZ USA Department of Psychiatry Harvard School of Medicine Cambridge MA USA Department of Management Science and Statistics University of Texas San Antonio TX USA Behavioral Neuropharmacology and Neuroimaging laboratory Clinical Research Institute on Addictions Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA Future Biologics Lawrenceville GA USA Department of Microbiology Immunology & Tropic Diseases School of Medicine Georgetown University Washington DC USA Department of Pharmaceutical Sciences College of Pharmacy Texas Southern University Houston TX USA Department of Psychiatry School of Medicine Case Western University Cleveland OH USA Brain and Behavior laboratory Curry College Milton MA USA The Neurogenesis Project Jacksonville FL USA Department of Family medicine Jefferson Health Northeast Philadelphia PA USA Departmen

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as

关键词： PANDAS CANS Genetic Addiction Risk Testing (GARS) Pro-Dopamine Regulation Hypodopaminergia Polymorphisms Antibacterial Therapy Infections

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Arrhythmias,chronic kidney disease and the elderly:a triple jeopardy

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Journal of Geriatric Cardiology 2005年第3期2卷 178-182页

作者： Abdul Wase Arvind Modawal wright state university school of medicine electrophysiology laboratory Good Samaritan Hospital and Health CenterDaytonOH 45406USA Department of Family medicine university of Cincinnati CincinnatiOH 45267USA

Crdiovascular diseases (CVD) incur a heavy burden of morbidity and mortality among patients with chronic kidney disease (CKD),particularly among the *** is estimated that about 22-25% of all adults beyond the age of 6... 详细信息

关键词： ESRD Arrhythmias,chronic kidney disease and the elderly QT

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Targeting autophagy as a therapeutic strategy for identification of liganans from Peristrophe japonica in Parkinson’s disease

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Signal Transduction and Targeted Therapy 2021年第3期6卷 596-598页

作者： An-Guo Wu Rong Pan Betty Yuen-Kwan Law Wen-Qiao Qiu Jian-Ming Wu Chang-Long He Vincent Kam-Wai Wong Chong-Lin Yu Xiao-Gang Zhou Da-Lian Qin Sichuan Key Medical laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaSchool of PharmacyDepartment of Human AnatomySchool of Preclinical MedicineEducation Ministry Key Laboratory of Medical ElectrophysiologySouthwest Medical UniversityLuzhou 646000China state Key laboratory of Quality Research in Chinese medicine Macao University of Science and TechnologyMacaoChina

Dear Editor,PD is characterized by the loss of dopaminergic neurons in substantia nigra,and the loss of dopamine resulting in motor deficit.1 Its main pathological hallmarks include the genetic mutations of gene such as a-synudein.2 Increasing study showed that the dopaminergic neurons in midbrain are sensitive and damaged by the PD toxins.

关键词： nude dopamine therapeutic

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High-throughput screening for amyloid-β binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC−DAD-Q/TOF-MS/MS

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1723-1739页

作者： Minsong Guo Fengdan Zhu Wenqiao Qiu Gan Qiao Betty Yuen-Kwan Law Lu Yu Jianming Wu Yong Tang Chonglin Yu Dalian Qin Xiaogang Zhou Anguo Wu Sichuan Key Medical laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaSchool of PharmacyEducation Ministry Key Laboratory of Medical ElectrophysiologySouthwest Medical UniversityLuzhou 646000China state Key laboratory of Quality Research in Chinese medicine Macao University of Science and TechnologyTaipaMacao 999078China Department of Neurosurgery Sichuan Provincial People’s Hospital University of Electronic Science and Technology of ChinaChengdu 610000China

Discovery of drugs rapidly and effectively is an important aspect for Alzheimer's disease(AD).In this study,a novel high-throughput screening(HTS)method aims at screening the small-molecules with amyloid-β(Aβ)binding affinity from natural medicines,based on the combinational use of biolayer interferometry(BLI)and ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time-of-flight tandem mass spectrometry(UHPLC−DAD-Q/TOF-MS/MS)has been firstly ***,the components in natural medicines disassociated from biotinylated Aβwere collected to analyze their potential Aβbinding affinity by UHPLC−DAD-Q/TOF-MS/***,baicalein was confirmed to exhibit the highest binding affinity with Aβin Scutellaria ***,polyporenic acid C(PPAC),dehydrotumulosic acid(DTA),and tumulosic acid(TA)in Kai-Xin-San(KXS)were also identified as potent Aβ*** bioactivity validations indicated that these compounds could inhibit Aβfibrillation,improve the viability in Aβ-induced PC-12 cells,and decrease the Aβcontent and improve the behavioral ability in Caenorhabditis *** molecular docking results confirmed that PPAC,DTA,and TA possessed good binding properties with Aβ.Collectively,the present study has provided a novel and effective HTS method for the identification of natural inhibitors on Aβfibrillation,which may accelerate the process on anti-AD drugs discovery and development.

关键词： Alzheimer’s disease High-throughput screening Biolayer interferometry UHPLCDAD-Q/TOFMS/MS Kai-Xin-San

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Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury

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Protein & Cell 2019年第8期10卷 566-590页

作者： Dandan Luo Weihong Ge Xiao Hu Chen Li Chia-Ming Lee Liqiang Zhou Zhourui Wu Juehua Yu Sheng Lin Jing Yu Wei Xu Lei Chen Chong Zhang Kun Jiang Xingfei Zhu Haotian Li Xinpei Gao Yanan Geng Bo Jing Zhen Wang Changhong Zheng Rongrong Zhu Qiao Yan Quan Lin Keqiang Ye Yi E.Sun Liming Cheng Division of Spine Surgery Department of Orthopedics Tongji Hospital Tongji University School of Medicine Institute of Spine and Spine Cord Injury of Tongji university Stem Cell Translational Research Center Tongji Hospital Tongji University School of Medicine Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine University of California Los Angeles Department of Pathology and laboratory medicine Center for neurodegeneration disease Emory University School of Medicine

The mammalian central nervous system(CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier(BBB). Yet,immune functions have been postulated to heavily infiuence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury(SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis(WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI,which was confirmed by immunohistochemical analysis and was consistent with better functional *** analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced infiammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

关键词： immune deficiency neurotransmision spinal cord injury repair transcriptomic analysis

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Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

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Protein & Cell 2021年第7期12卷 545-556页

作者： Dandan Liang Zhigang Xue Jinfeng Xue Duanyang Xie Ke Xiong Huixing Zhou Fulei Zhang Xuling Su Guanghua Wang Qicheng Zou Yi Liu Jian Yang Honghui Ma Luying Peng Chunyu Zeng Gang Li Li Wang Yi-Han Chen Department of Cardiology East HospitalTongji University School of MedicineShanghai 200120China Key laboratory of Arrhythmias of the Ministry of Education of China Tongji University School of MedicineShanghai 200120China Institute of Medical Genetics Tongji UniversityShanghai 200092China Department of Regenerative medicine Tongji University School of MedicineShanghai 200092China Reproductive medicine Center Tongji HospitalTongji University School of MedicineShanghai 200065China Department of Pathology and Pathophysiology Tongji University School of MedicineShanghai 200092China Department of Cardiology Daping HospitalChongqing 400042China Department of Neurology East HospitalTongji University School of MedicineShanghai 200120China state Key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Activation of the heart normally begins in the sinoatrial node(SAN).Electrical impulses spontaneously released by SAN pacemaker cells(SANPCs)trigger the contraction of the ***,the cellular nature of SANPCs remains ***,we report that SANPCs exhibit glutamatergic neuron-like *** comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse,we found that SANPCs co-clustered with cortical *** and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system,expressing genes encoding glutamate synthesis pathway(G/s),ionotropic and metabotropic glutamate receptors(Grina,Gria3,Grm1 and Grm5)t and glutamate transporters(Slc17a7).SANPCs highly expressed cell markers of glutamatergic neurons(Snap25 and S/-c17a7)t whereas Gad1,a marker of GABAergic neurons,was *** studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca2+transients frequency in single ***,our work suggests that SANPCs share dominant biological properties with glutamatergic neurons,and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm,which provides a potential intervention target for pacemaker cell-associated arrhythmias.

关键词： sinoatrial node pacemaker cell glutamatergic neuron single-cell RNA-seq electrophysiology

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