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Do pyroptosis, apoptosis, and necroptosis (PANoptosis) exist in cerebral ischemia? Evidence from cell and rodent studies

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Neural Regeneration Research 2022年第8期17卷 1761-1768页

作者： wei-tao yan yan-Di yang Xi-Min Hu Wen-Ya Ning Lyu-Shuang Liao Shuang Lu Wen-Juan Zhao Qi Zhang Kun Xiong Department of Neurobiology and Human Anatomy School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Human Resources Third Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all the components of PANoptosis to be regulated simultaneously.PANoptosis provides a new way to study the regulation of cell death,in that different types of cell death may be regulated at the same time.To test whether PANoptosis exists in diseases other than infectious diseases,we chose cerebral ischemia/reperfusion injury as the research model,collected articles researching cerebral ischemia/reperfusion from three major databases,obtained the original research data from these articles by bibliometrics,data mining and other methods,then integrated and analyzed these data.We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion.In the cell model simulating ischemic brain injury,pyroptosis,apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons.Pyroptosis,apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury.This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.

关键词： apoptosis brain central nervous system ischemia/reperfusion middle cerebral artery occlusion necroptosis oxygen and glucose deprivation PANoptosis pyroptosis regulated cell death

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PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons

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Neural Regeneration Research 2023年第2期18卷 357-363页

作者： wei-tao yan Wen-Juan Zhao Xi-Min Hu Xiao-Xia Ban Wen-Ya Ning Hao Wan Qi Zhang Kun Xiong Department of Human Anatomy and Neurobiology School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Human Resources Third Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina Key Laboratory of Emergency and Trauma Ministry of EducationCollege of Emergency and TraumaHainan Medical UniversityHaikouHainan ProvinceChina

PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

关键词： apoptosis gasdermin-D(GSDMD) ischemia/reperfusion mixed lineage kinase domain-like protein(MLKL) necroptosis NOD-like receptor protein 3(NLRP3) PANoptosis pyroptosis receptor-interacting protein kinase 3(RIPK3) retinal neuron

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Research trends, hot spots and prospects for necroptosis in the field of neuroscience

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Neural Regeneration Research 2021年第8期16卷 1628-1637页

作者： wei-tao yan Shuang Lu yan-Di yang Wen-Ya Ning yan Cai Xi-Min Hu Qi Zhang Kun Xiong Department of Anatomy and Neurobiology School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Third Xiangya Hospital of Central South University ChangshaHunan ProvinceChina Department of Histology and Embryology School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

There are two types of cell death-apoptosis and necrosis. Apoptosis is cell death regulated by cell signaling pathways, while necrosis has until recently been considered a passive mechanism of cell death caused by environmental pressures. However, recent studies show that necrosis can also be regulated by specific cell signaling pathways. This mode of death, termed necroptosis, has been found to be related to the occurrence and development of many diseases. We used bibliometrics to analyze the global output of literature on necroptosis in the field of neuroscience published in the period 2007–2019 to identify research hotspots and prospects. We included 145 necroptosisrelated publications and 2239 references published in the Web of Science during 2007–2019. Visualization analysis revealed that the number of publications related to necroptosis has increased year by year, reaching a peak in 2019. China is the country with the largest number of publications. Key word and literature analyses demonstrated that mitochondrial function change, stroke, ischemia/reperfusion and neuroinflammation are likely the research hotspots and future directions of necroptosis research in the nervous system. The relationship between immune response-related factors, damage-associated molecular patterns, pathogen-associated molecular patterns and necroptosis may become a potential research hotspot in the future. Taken together, our findings suggest that although the inherent limitations of bibliometrics may affect the accuracy of the literature-based prediction of research hotspots, the results obtained from the included publications can provide a reference for the study of necroptosis in the field of neuroscience.

关键词： bibliometric analysis citations CiteSpace h-index necroptosis network analysis neuroscience output VOSviewer Web of Science

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RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39℃

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Neural Regeneration Research 2020年第5期15卷 865-874页

作者： Li-Min Guo Zhen Wang Shi-Ping Li Mi Wang wei-tao yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie yan Kun Xiong Department of Neurobiology and Human Anatomy School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Department of Basic Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu ProvinceChina Department of Neurology People’s Hospital of LianhuaPingxiangJiangxi ProvinceChina Department of Human Anatomy School of Basic Medical ScienceXinjiang Medical UniversityUrumqiXinjiang Uygur Autonomous RegionChina Department of Forensic Science School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Narcotics Division Municipal Security BureauChangshaHunan ProvinceChina

Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.

关键词： GSK'872 human brain tissue hyperpyrexia methamphetamine mixed lineage kinase domain-like protein necrostatin-1 necroptosis nerve regeneration neural regeneration rat cortical neurons receptor-interacting protein-3 synergistic effect

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Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

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World Journal of Diabetes 2024年第3期15卷 378-391页

作者： yan Yi tao Wang wei Xu San-Hong Zhang Department of Ultrasonography The First Affiliated Hospital of Yangtze UniversityJingzhou 434000Hubei ProvinceChina Clinical Molecular Immunology Center Yangtze UniversityJingzhou 434023Hubei ProvinceChina Department of Pediatric Xiantao First People’s HospitalXiantao 433000Hubei ProvinceChina

Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

关键词： Gestational diabetes mellitus Placental functions Epigenetics Offspring development

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Tunable VO_(2) cavity enables multispectral manipulation from visible to microwave frequencies

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Light(Science & Applications) 2024年第3期13卷 510-518页

作者： Hang wei Jinxin Gu tao Zhao Zhiyuan yan He-Xiu Xu Shuliang Dou Cheng-wei Qiu Yao Li Center for Composite Materials and Structure Harbin Institute of TechnologyHarbin 150001China National University of Singapore Department of Electrical&Computer EngineeringSingapore 117583Singapore School of Chemical Engineering and Technology Harbin Institute of TechnologyHarbin 150001China Suzhou Laboratory Suzhou 215123China

Optical materials capable of dynamically manipulating electromagnetic waves are an emerging field in memories,optical modulators,and thermal management.Recently,their multispectral design preliminarily attracts much attention,aiming to enhance their efficiency and integration of functionalities.However,the multispectral manipulation based on these materials is challenging due to their ubiquitous wavelength dependence restricting their capacity to narrow wavelengths.In this article,we cascade multiple tunable optical cavities with selective-transparent layers,enabling a universal approach to overcoming wavelength dependence and establishing a multispectral platform with highly integrated functions.Based on it,we demonstrate the multispectral(ranging from 400 nm to 3 cm),fast response speed(0.9 s),and reversible manipulation based on a typical phase change material,vanadium dioxide.Our platform involves tandem VO_(2)-based Fabry–Pérot(F-P)cavities enabling the customization of optical responses at target bands independently.It can achieve broadband color-changing capacity in the visible region(a shift of~60 nm in resonant wavelength)and is capable of freely switching between three typical optical models(transmittance,reflectance,and absorptance)in the infrared to microwave regions with drastic amplitude tunability exceeding 0.7.This work represents a state-of-art advance in multispectral optics and material science,providing a critical approach for expanding the multispectral manipulation ability of optical systems.

关键词： spectral microwave visible

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Ultrasound-guided continuous adductor canal block for analgesia after total knee replacement

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Chinese Medical Journal 2014年第23期127卷 4077-4081页

作者： Zhang wei Hu yan tao yan Liu Xuebing Wang Geng Department of Anesthesiology Beijing Jishuitan Hospital Beijing 100035 China

Background There are several methods for postoperative analgesia for knee surgery.The commonly utilized method is multimodal analgesia based on continuous femoral nerve block.The aim of this study was to investigate the application of continuous adductor canal block for analgesia after total knee replacement and compare this method with continuous femoral nerve block.Methods Sixty patients scheduled for total knee replacement from June 2013 to March 2014 were randomly divided into a femoral group and an adductor group.Catheters were placed under the guidance of nerve stimulation in the femoral group and under the guidance of ultrasound in the adductor group.Operations were performed under combined spinal and epidural anesthesia.After the operations,0.2％ ropivacaine was given at a speed of 5 ml/h through catheters in all patients.Visual analogue scale （VAS） pain scores at rest and while moving were noted at 4,24,and 48 hours after the operation,and quadriceps strength was also assessed at these time-points.Secondary parameters such as doses of complementary analgesics and side effects were also recorded.Results There were no significant differences between the groups in VAS pain scores at rest or while moving,at 4,24,or 48 hours after the operation （P ＞0.05）.At these time-points,mean quadriceps strengths in the adductor group were 3.0 （2.75-3.0）,3.0 （3.0-4.0）,and 4.0 （3.0-4.0）,respectively,all of which were significantly stronger than the corresponding means in the femoral group,which were 2.0 （2.0-3.0）,2.0 （2.0-3.0）,and 3.0 （2.0-4.0）,respectively （P ＜0.05）.There were no significant differences between the groups in doses of complementary analgesics or side effects （P ＞0.05）.X-ray images of some patients showed that local anesthetic administered into the adductor canal could diffuse upward and reach the femoral triangle.Conclusions Continuous adductor canal block with 0.2％ ropivacaine could be used effectively for analgesia after total knee replacement.Compared with continuous femoral nerve block,this analgesic me

关键词： adductor canal block femoral nerve block ropivacaine total knee replacement multimodal analgesia

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Distributed Minimum-Energy Containment Control of Continuous-Time Multi-Agent Systems by Inverse Optimal Control

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IEEE/CAA Journal of Automatica Sinica 2024年第6期11卷 1533-1535页

作者： Fei yan Xiangbiao Liu tao Feng School of Information Science and Technology Southwest Jiaotong UniversityChengdu 611756China National Engineering Laboratory of Integrated Transportation Big Data Application Technology Chengdu 611756China

Dear Editor,This letter focuses on the distributed optimal containment control of continuous-time multi-agent systems(CTMASs)with respect to the minimum-energy performance index over fixed topology.To achieve this,we firstly investigate the optimal containment control problem using the inverse optimal control method,where all states of followers asymptotically converge to the convex hull spanned by the leaders while some quadratic performance indexes get minimized.A sufficient condition for existence of the distributed optimal containment control protocol is derived.By introducing the parametric algebraic Riccati equation(PARE),it is strictly proved that the global performance index can be used to approximate the standard minimumenergy performance index as the parameters tends to infinity.In consequence,the standard minimum-energy cooperative containment control can be solved by local steady state feedback protocols.

关键词： optimal infinity algebraic

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Exploring the autophagy-related pathogenesis of active ulcerative colitis

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World Journal of Clinical Cases 2024年第9期12卷 1622-1633页

作者： Zhuo-Zhi Gong Teng Li He yan Min-Hao Xu Yue Lian Yi-Xuan yang wei wei tao Liu Wangjing Hospital China Academy of Chinese Medical SciencesBeijing 100102China College of Traditional Chinese Medicine School of Traditional Chinese MedicineBeijing 100102China Guang’anmen Hospital China Academy of Chinese Medical SciencesBeijing 100053China

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

关键词： Ulcerative colitis Autophagy Bioinformatic Targets Pathogenesis

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Predict the evolution of mechanical property of Al-Li alloys in a marine environment

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Defence Technology（防务技术） 2024年第1期31卷 557-566页

作者： wei Li Lin Xiang Guang Wu Hongli Si Jinyan Chen Yiming Jin yan Su Jianquan tao Chunyang Huang State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing100036China Chongqing Innovation Center Beijing Institute of TechnologyChongqing400044China First Research Institute of the Ministry of Public Security for PR China Beijing100036China Southwest Technology and Engineering Research Institute Chongqing400039China

The ocean is one of the essential fields of national defense in the future,and more and more attention is paid to the lightweight research of Marine equipment and materials.This study it is to develop a Machine learning(ML)-based prediction method to study the evolution of the mechanical properties of Al-Li alloys in the marine environment.We obtained the mechanical properties of Al-Li alloy samples under uniaxial tensile deformation at different exposure times through Marine exposure experiments.We obtained the strain evolution by digital image correlation(DIC).The strain field images are voxelized using 2D-Convolutional Neural Networks(CNN)autoencoders as input data for Long Short-Term Memory(LSTM)neural networks.Then,the output data of LSTM neural networks combined with corrosion features were input into the Back Propagation(BP)neural network to predict the mechanical properties of Al-Li alloys.The main conclusions are as follows:1.The variation law of mechanical properties of2297-T8 in the Marine atmosphere is revealed.With the increase in outdoor exposure test time,the tensile elastic model of 2297-T8 changes slowly,within 10%,and the tensile yield stress changes significantly,with a maximum attenuation of 23.6%.2.The prediction model can predict the strain evolution and mechanical response simultaneously with an error of less than 5%.3.This study shows that a CNN/LSTM system based on machine learning can be built to capture the corrosion characteristics of Marine exposure experiments.The results show that the relationship between corrosion characteristics and mechanical response can be predicted without considering the microstructure evolution of metal materials.

关键词： Marine environment Al-Li alloy Machine learning Corrosion

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