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TREM-1 mediates interaction between substantia nigra microglia and peripheral neutrophils

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Neural Regeneration Research 2024年第6期19卷 1375-1384页

作者： Tong Shen Guiyun Cui Hao Chen Long Huang Wei Song Jie Zu Wei Zhang Chuanying Xu Liguo Dong Yongmei Zhang jiangsu province key laboratory of Anesthesiology Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina jiangsu province key laboratory of Anesthesia and Analgesia Application Technology Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina NMPA key laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs XuzhouJiangsu ProvinceChina Department of Neurology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's *** receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate *** this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and *** a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia ***,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal ***,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil ***,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide *** found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil ***,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by ***-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with *** findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.

关键词： 1-methyl-4-phenylpyridiniumion dopaminergic neurons infiltration 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine microglia neutrophils neuroinflammation Parkinson's disease SYK TREM-1

Immune functions of C-type lectins in medical arthropods

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Insect Science 2024年第3期31卷 652-662页

作者： Zhihao Ming Zhiqiang Chen Hao Tong Xia Zhou Tingting Feng Jianfeng Dai Institute of biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhouJiangsu ProvinceChina School of biology and Basic Medical Science Suzhou Medical College of Soochow UniversitySuzhouJiangsu ProvinceChina

C-type lectins(CTLs)are a family of proteins that contain 1 or more carbohydrate-recognition domains(CRDs)and bind to a broad repertoire of ligands in the presence of calcium *** play important roles in innate immune defenses against microorganisms by acting as pattern-recognition receptors(PRRs)for invading pathogens,such as bacteria,viruses,and *** binding to pathogen-associated ligands,CTLs mediate immune responses,such as agglutination,phagocytosis,and the activation of phenol oxidase progenitors,thereby clearing *** are an evolutionarily conserved family found in almost all vertebrates and *** arthropods can acquire and transmit a range pathogens through various approaches,such as bloodsucking,lancing,and parasitism,thus infecting humans and animals with related diseases,some of which can be *** studies have shown that lectins are important components of the arthropod immune system and are essential for the immune responses of arthropods to arthropod-borne *** article reviews the current understanding of the structure,function,and signaling pathways involved in CTLs derived from important medical arthropods.

关键词： arthropod C-type lectin innate immunity vector-borne disease

Targeting Haemaphysalis longicornis serpin to prevent tick feeding and pathogen transmission

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Insect Science 2024年第3期31卷 694-706页

作者： Tingting Feng Hao Tong Qianqian Zhang Zhihao Ming Zhenyu Song Xia Zhou Jianfeng Dai Institute of biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhouJiangsu ProvinceChina School of biology and Basic Medical Science Suzhou Medical College of Soochow UniversitySuzhouJiangsu ProvinceChina

Serine proteinase inhibitors(serpins),identified from the hard tick Haemaphysalis longicornis of China,play significant roles in various animal physiological *** this study,we showed that *** serpins(Hlserpin-a and Hlserpin-b)were induced during blood-feeding in nymph ticks and exhibited anticoagulation activity in *** Hlserpins through RNA interference(RNAi)significantly impaired tick *** of mice with recombinant Hlserpins or passive transfer of Hlserpin antiserum significantly curtails the efficacy of tick ***,the transmission of the Langat virus(LGTV)from ticks to mice witnessed a substantial decrease when Hlserpins were *** findings suggest that inhibiting Hlserpins can hamper tick engorgement and pathogen transmission,indicating the potential of Hlserpins as a vaccine to countertick-borne diseases.

关键词： feeding LGTV serpin TBEV tick

Brain-inspired chaotic spiking backpropagation

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National Science Review 2024年第06期11卷 169-179页

作者： Zijian Wang Peng Tao Luonan Chen key laboratory of Systems Health Science of Zhejiang province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences key laboratory of Systems biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Guangdong Institute of Intelligence Science and Technology Pazhou laboratory(Huangpu)

Spiking neural networks(SNNs) have superior energy efficiency due to their spiking signal transmission,which mimics biological nervous systems, but they are difficult to train effectively. Although surrogate gradient-based methods offer a workable solution, trained SNNs frequently fall into local minima because they are still primarily based on gradient dynamics. Inspired by the chaotic dynamics in animal brain learning, we propose a chaotic spiking backpropagation(CSBP) method that introduces a loss function to generate brain-like chaotic dynamics and further takes advantage of the ergodic and pseudo-random nature to make SNN learning effective and robust. From a computational viewpoint, we found that CSBP significantly outperforms current state-of-the-art methods on both neuromorphic data sets(***-CIFAR10 and DVS-Gesture) and large-scale static data sets(e.g. CIFAR100 and Image Net) in terms of accuracy and robustness. From a theoretical viewpoint, we show that the learning process of CSBP is initially chaotic, then subject to various bifurcations and eventually converges to gradient dynamics,consistently with the observation of animal brain activity. Our work provides a superior core tool for direct SNN training and offers new insights into understanding the learning process of a biological brain.

关键词： spiking neural networks surrogate gradient local minima backpropagation brain-inspired learning chaos

Tau truncation in the pathogenesis of Alzheimer's disease:a narrative review

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Neural Regeneration Research 2024年第6期19卷 1221-1232页

作者： Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu key laboratory of Neuroregeneration of jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsCoinnovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Department of biochemistry and molecular biology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Clinical Pharmacy Affiliated Maternity and Child Health Care Hospital of Nantong UniversityNantong UniversityNantongJiangsu ProvinceChina laboratory of Animal Center Nantong UniversityNantongJiangsu ProvinceChina Department of Neurochemistry Inge Grundke-Iqbal Research FloorNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandNYUSA

Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau *** studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease *** physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like *** addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent *** review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.

关键词： Alzheimer's disease cleavage site diagnosis marker neurofibrillary tangles phosphorylation Tau Tau aggregation therapy truncation

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2024年第9期19卷 2081-2088页

作者： Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng Xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng Chun-Feng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina jiangsu key laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Xuzhou Central HospitalXuzhouJiangsu ProvinceChina jiangsu key laboratory of Neuropsychiatric Disease and Institute of Neuroscience Soochow UniversitySuzhouJiangsu ProvinceChina

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal *** dysfunction can precede the onset of motor symptoms by several *** microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain ***/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease *** this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota *** found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor ***,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with ***,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and *** of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier *** results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s ***,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that c

关键词： C/EBP/AEP signaling pathway endotoxemia fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease

“Three-in-one” strategy of trifluoromethyl regulated blood-brain barrier permeable fluorescent probe for peroxynitrite and antiepileptic evaluation of edaravone

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Chinese Chemical Letters 2024年第10期35卷 360-363页

作者： Lei Shen Hongmei Liu Ming Jin Jinchao Zhang Caixia Yin Shuxiang Wang Yutao Yang key laboratory of Medicinal Chemistry and molecular Diagnosis of the Ministry of Education Chemical Biology Key Laboratory of Hebei ProvinceState Key Laboratory of New Pharmaceutical Preparations and ExcipientsCollege of Chemistry and Materials ScienceHebei UniversityBaoding 071002China key laboratory of Chemical biology and molecular Engineering of Ministry of Education Institute of Molecular ScienceShanxi UniversityTaiyuan 030006China

Epilepsy,as a chronic neurological disease of the brain,is closely related to oxidative stress,and the peroxynitrite(ONOO-)significantly rise up in this ***,ONOO-is considered as a potential biomarker for early prediction of ***,some potential diagnostic reagents for epilepsy are hindered by the blood-brain barrier(BBB).Meanwhile,“drug repurposing”is attracting a growing ***(EDA),as a first-line drug in the clinical treatment of cerebral ischemia,plays antioxidant roles in scavenging free radicals,promising potential antiepileptic ***,it is imperative to develop fluorescent probes for monitoring ONOO-fluctuations in the epileptic ***,we proposed a novel fluorescent probe with the thiocarbonate as the promising recognition unit for ONOO-and dicyanoisophorone derivative as the ***,by the“three-in-one”strategy,the introduction of trifluoromethyl into DCI-ONOO-3 can extend the emission wavelength of the fluorophore,shorten the response and increase ***,DCI-ONOO-3 was used for monitoring ONOO-fluxes in brain of epileptic mice and evaluating the antiepileptic efficacy of *** opens up a new way for the design of BBB permeable fluorescent probes,and provides a convincing new method for the diagnosis and treatment of epilepsy.

关键词： Fluorescent probe Blood-brain barrier Peroxynitrite Epilepsy Drug repurposing

Establishment and transcriptome analysis of single blastomerederived cell lines from zebrafish

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Journal of Genetics and Genomics 2024年第9期51卷 957-969页

作者： Jia Xu Siqi Liu Yirui Ai Yunbin Zhang Shifeng Li Yiping Li key laboratory of Multi-Cell Systems Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

Maintaining chromosome euploidy in zebrafish embryonic cells is challenging because of the degradation of genomic integrity during cell *** this study,we report the derivation of zebrafish cell lines from single *** cell lines have a stable chromosome status attributed to BMP4 and exhibit continuous proliferation in *** zebrafish cell lines are successfully established from single ***-cell transcriptome sequencing analysis confirms the fidelity of gene expression profiles throughout long-term culturing of at least 45 *** long-term cultured cells are specialized into epithelial cells,exhibiting similar expression patterns validated by integrative transcriptomic ***,this work provides a protocol for establishing zebrafish cell lines from single blastomeres,which can serve as valuable tools for in vitro investigations of epithelial cell dynamics in terms of lifeedeath balance and cell fate determination during normal homeostasis.

关键词： Zebrafish Single embryo Cell lines Sngle-cell RNA sequencing(scRNA-Seq) Embryonic epidermis Epithelium

Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor

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Chinese Chemical Letters 2024年第8期35卷 221-224页

作者： Xiaohong Wen Mei Yang Lie Li Mingmin Huang Wei Cui Suping Li Haiyan Chen Chen Li Qiuping Guo College of biology State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China

Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer ***,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor ***,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor *** En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA *** En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor *** strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.

关键词： Enzyme-controlled APE1 DNA tetrahedron Cancer-specific ATP biosensing