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Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

Bioinspired nanotransducers for neuromodulation

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Nano Research 2024年第2期17卷 618-632页

作者： Fan Yang Xiang Wu Sa Cai Guosong Hong Department of Materials Science and Engineering Stanford UniversityStanfordCA 94305USA Wu Tsai Neurosciences Institute Stanford UniversityStanfordCA 94305USA School of Science Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China

The field of neuromodulation has experienced significant advancements in the past decade,owing to breakthroughs in disciplines such as materials science,genetics,bioengineering,photonics,and *** convergence of these fields has resulted in the development of nanotransducers,devices that harness the synergies of these diverse *** nanotransducers,essential for neuromodulation,often draw inspiration from energy conversion processes found in nature for their unique *** this review,we will delve into the latest advancements in wireless neuromodulation facilitated by optical,magnetic,and mechanical *** will examine their working principles,properties,advantages,and limitations in comparison to current methods for deep brain neuromodulation,highlighting the impact of natural systems on their design and ***,we will underscore potential future directions,emphasizing how continued progress in materials science,neuroscience,and bioengineering might expand the horizons of what is achievable with nanotransducer-enabled neuromodulation.

关键词： bioinspired synthesis neuromodulation mechanoluminescence focused ultrasound nanotransducers sono-optogenetics

Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope

CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden university medical center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

Size matters:the biochemical logic of ligand type in endocrine crosstalk

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Life Metabolism 2024年第1期3卷 10-20页

作者： Jameel Barkat Lone Jonathan Z.Long Katrin J.Svensson Department of Pathology Stanford University School of MedicineStanfordCA 94305United States Department of Chemistry Stanford UniversityStanfordCA 94305United States stanford Diabetes Research center Stanford University School of MedicineStanfordCA 94305United States Sarafan ChEM-H Stanford UniversityStanfordCA 94305United States Wu Tsai Human Performance Alliance Stanford UniversityStanfordCA 94305United States stanford Cardiovascular Institute Stanford University School of MedicineCA 94305United States

The endocrine system is a fundamental type of long-range cell-cell communication that is important for maintaining metabolism,physiology,and other aspects of organismal *** signaling is mediated by diverse blood-borne ligands,also called hormones,including metabolites,lipids,steroids,peptides,and *** size and structure of these hormones are fine-tuned to make them bioactive,responsive,and adaptable to meet the demands of changing *** has nature selected such diverse ligand types to mediate communication in the endocrine system?What is the chemical,signaling,or physiologic logic of these ligands?What fundamental principles from our knowledge of endocrine communication can be applied as we continue as a field to uncover additional new circulating molecules that are claimed to mediate long-range cell and tissue crosstalk?This review provides a framework based on the biochemical logic behind this crosstalk with respect to their chemistry,temporal regulation in physiology,specificity,signaling actions,and evolutionary development.

关键词： endocrine ligand size metabolites signaling evolution

Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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Science China Chemistry 2024年第2期67卷 517-522页

作者： Xianbao Sun Manli Wang Xiaoyang Liu Wenjun Zhan Guangqiong Xu Qiaochu Jiang Hai-Dong Xu Fuqiang Wang Gaolin Liang State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Analysis center Nanjing Medical UniversityNanjing210029China

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains ***,we proposed an enzymatic self-assembly/disassembly strategy to address this issue.A peptide molecule Nap FFEYIH(YH) was rationally designed which,after self-assembling into nanofibers,lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase *** dephosphorylation of Nap FFEYp IH(Yp H) by alkaline phosphatase to yield YH also turned “ON” the hydrolase *** turn,phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield Yp H disassembled the nanofibers and thus turned the activity “OFF”.As such,the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine *** work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

关键词： disassembly hydrolytic activity mimetic enzyme phosphorylation self-assembly

The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

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Animal Models and Experimental Medicine 2024年第3期7卷 388-395页

作者： Meng Li Panpan Wei Kexin Li Haole Liu Naqash Alam Haiwen Hou Jie Deng Baohui Xu Enqi Liu Sihai Zhao Yankui Li Laboratory Animal center Xi'an Jiaotong UniversityXi'anChina Department of Vascular Surgery The Second Hospital of Tianjin Medical UniversityTianjinChina Department of Cardiology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina Department of Vascular Surgery Stanford University School of MedicineStanfordCaliforniaUSA

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial *** occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse *** study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA *** IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were *** 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant *** mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH *** was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe ***,only a lower numbers of T cells and B cells were found in the IH *** cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe *** conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA *** will help researchers better understand this model,and optimize it for use in AAA-related research.

关键词： abdominal aortic aneurysms animal model histology intimal hyperplasia

Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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Research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao Zhang Yupeng Cun Weixiang Chen Yang Yang Qian Zhang Huanhuan Li Jun Zhong Xuyang Zhang Hua Feng Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina medical Research center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(NPCs)has been shown to be an effective treatment for ischemic ***,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after *** acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic ***,the role of ASIC1a in NPCs post-ischemia remains ***,our results indicated that ASIC1a was expressed in NPCs with channel functionality,which could be activated by extracellular *** evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of *** vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

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World Journal of Clinical Cases 2024年第14期12卷 2342-2349页

作者： Yuto Suzuki Yasumi Katayama Yo Fujimoto Ikuhiro Kobori Masaya Tamano Department of Gastroenterology Dokkyo medical University Saitama Medical CenterKoshigayaSaitama 343-8555Japan Endoscopy center Dokkyo Medical University Saitama Medical CenterKoshigayaSaitama 343-8555Japan

BACKGROUND Helicobacter pylori(***)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after *** ***,it would be extremely useful if GC could be predicted after *** Kyoto classification score for gastritis(GA)is closely related to cancer ***,how the score for GC changes after eradication before onset is not well *** To investigate the characteristics of the progression of Kyoto classification scores for GC after *** *** Eradication of *** was confirmed in all patients using either the urea breath test or the stool antigen *** Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years *** ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA *** In total,30 cases of early GC and 30 cases of chronic GA were *** pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated *** total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after *** with severe atrophy after *** eradication require careful monitoring.

关键词： Helicobacter pylori Kyoto classification Gastritis Eradication therapy Gastric cancer