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Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

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Neural Regeneration Research 2025年第8期20卷 2325-2336页

作者： Yafan Bai Hui Ma Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li Department of Anesthesiology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing Institute of Basic Medical Sciences BeijingChina Hebei North University ZhangjiakouHebei ProvinceChina Beijing Institute of Pharmacology and toxicology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijingChina

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary *** this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain *** experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain ***,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 ***,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain ***,YL-0919 effectively combated oxidative stress both in vivo and in *** protective effects of YL-0919 were partially inhibited by *** results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist ***-0919 may have potential as a new treatment for traumatic brain injury.

关键词： antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury

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Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

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Science China Chemistry 2025年第01期 377-384页

作者： Shiwen Liu Xuerui Wan Meng Zhao Jiaqi Wang Weilan Wu Linlin You Yonggui Yuan Qian Xu Rong Gao key laboratory of Environmental Medicine Engineering Ministry of Education School of Public Health Southeast University key laboratory of Modern toxicology of Ministry of Education Department of Hygienic Analysis and Detection School of Public HealthNanjing Medical University Department of Psychosomatics and Psychiatry Zhongda Hospital School of Medicine Southeast University

The measurement of amino acid and monoamine neurotransmitters（NTs） in serum plays a central role in the identification and monitoring of clinical panic disorder（PD）. However, the strong polarity and chemical heterogeneity of NTs make direct extraction and rapid detection extremely challenging. Herein, we developed a strategy that integrated solid phase extraction based on magnetic Fe3O4coated with polydopamine（Fe3O4@PDA） and direct analysis of mass spectrometry in real time（DART-MS） for quantification of 10 NTs. We systematically investigated the optimal conditions of this strategy to achieve good accuracy and precision. Compared with existing magnetic solid phase extraction methods for NTs detection in biological samples, this strategy could adsorb more targets while having similar adsorption efficiencies, and the total process time was reduced by an average of 69.42%. We rapidly determined the metabolic abnormality of 6 types of NTs in the serum of PD patients and demonstrated their diagnostic accuracy. In addition, an outstanding feature of PD in which tryptophan was more metabolized by the KYN pathway and the 5-hydroxytryptamine pathway was inhibited could be elucidated by this strategy. Our results highlighted the potential ability of Fe3O4@PDA coupled with DART-MS to assist in the clinical diagnosis of PD.

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Decline and fall of aging astrocytes:the human perspective

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Neural Regeneration Research 2025年第6期20卷 1713-1714页

作者： Alexei Verkhratsky Alexey Semyanov Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Department of Neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of forensic Analytical toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania International Collaborative Center on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Department of Physiology Jiaxing University College of MedicineJiaxingZhejiang ProvinceChina

“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.

关键词： aging teeth progressive

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Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage

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Neural Regeneration Research 2025年第4期20卷 1015-1030页

作者： Ruoyu Huang Qiuyu Pang Lexin Zheng Jiaxi Lin Hanxi Li Lingbo Wan Tao Wang Department of forensic Science School of Basic Medicine and Biological SciencesSuzhou Medicine College of Soochow UniversitySuzhouJiangsu ProvinceChina

Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and *** plays a key role in the establishment and maintenance of the central nervous *** brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and *** brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental ***,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system *** hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and *** cholesterol levels are associated with the risk of intracerebral ***,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell *** cholesterol accumulation in the brain has been found after intracerebral *** this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell *** also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

关键词： cell death cholesterol metabolism intracerebral hemorrhage myelination therapeutic target

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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional Medicine Research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng Chen Yu-Chun Xie Department of Rehabilitation Medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian key laboratory of Toxicant and Drug toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAD family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

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Current status of hair analysis in forensic toxicology in China

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forensic Sciences Research 2021年第4期6卷 240-249页

作者： Hui Yan Ping Xiang Min Shen Department of forensic toxicology academy of Forensic scienceshanghai Key Laboratory of Forensic Medicineshanghaichina

Hair analysis has been mainly used to document drug use history in abusers,drug-facilitated crime cases,doping control analysis and postmortem toxicology in the fields of forensic toxicology,clinical toxicology,and doping *** analysis has also gained more attention in the last 30 years in *** technology has been promoted as more research has appeared concerning hair analysis,and consensus has been sought among forensic toxicologists regarding aspects such as hair decontamination treatment,detection of abused substances in hair,segmental hair analysis and interpretation of analytical ***,there are still some limitations in the estimation of drug intake time and frequency by segmental hair analysis due to the different growth cycles evident within a bundle of hairs,the drug incorporation mechanism and sampling *** and imaging mass spectrometry(iMS)technology based on a single hair may be a good choice to estimate drug intake time more *** of hair root samples may also be used to document acute poisoning in postmortem toxicology,and the analysis of the hair shaft can document long-term use of drugs depending on the length of the hair being evaluated.

关键词： forensic sciences forensic toxicology hair analysis black hair drug abuse microsampling imaging mass spectrometry

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Anticoagulant rodenticide intoxication in east China:a three-year analysis

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forensic Sciences Research 2016年第1期1卷 22-27页

作者： Hui Yan Lin Zhu Xianyi Zhuo Min Shen Ping Xiang Department of forensic toxicology Shanghai Key Laboratory of Forensic MedicineShanghai Forensic Service PlatformInstitute of Forensic ScienceMinistry of JusticePRCShanghaiChina

The study was designed to analyze the incidence and pattern of anticoagulant rodenticide intoxication in east China and to discuss strategies of diagnosis based on laboratory analysis experience.A total of 117 patients with anticoagulant rodenticide poisoning confirmed by toxicological analysis in east China were included in this study from 2011 to *** mean concentration of anticoagulant rodenticide,age,and gender of these patients,as well as the mode and type of poisoning,were *** age ranged from less than 1 to 80 years with the feeble preponderance of males(M D 53.0%,F D 47.0%).The 0–9 age group covered the largest ratio of these anticoagulant rodenticide poisoning *** or voluntary ingestion seems to be the most common cause of intoxication,with still the poisoning cause being unknown for a large number of positive *** was the most commonly observed anticoagulant rodenticide found in the biological samples,followed by *** concentrations of bromadiolone and brodifacoum that were detected in the first collected whole blood from each patient ranged from 1 to 878 ng/mL(mean 97.9 ng/mL)and from 0.5 to 1566 ng/mL(mean 225.1 ng/mL),*** data analysis shows a high incidence of anticoagulant rodenticide poisoning without awareness of the poisoned subjects,clearly emphasizing the need for toxicological analysis in patients with vitamin K-dependent coagulation disorder and restriction on availability of anticoagulant rodenticide.

关键词： forensic science forensic toxicology anticoagulant rodenticides intoxication bromadiolone brodifacoum poisoning

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Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant

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Military Medical Research 2019年第1期6卷 78-88页

作者： Xiao-rui Zhang Wen-xia Zhou Yong-xiang Zhang State key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology

AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. Research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.

关键词： Catalytic antioxidant Metalloporphyrins Chemical warfare agent Radiation damage Pharmacodynamics Pharmacokinetics

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Development of forensic standards in China: a review

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forensic Sciences Research 2022年第1期7卷 1-10页

作者： Xiaodan He Chengtao Li Shanghai key laboratory of forensic Medicine Key Laboratory of Forensic ScienceAcademy of Forensic ScienceMinistry of JusticeShanghaiChina

forensic science is crucial for the administration of justice and case *** China,political-legal organizations,including the courts,public security,procuratorate,and judicial administration,developed their own forensic practices before *** a result,the frequent and repeated appraisals undermined judicial authority and ***,a law was published in 2005 to improve the uniform forensic management system by the Standing Committee of the National People’s Congress,leading to the establishment of the forensic Administration of the Ministry of Justice in *** this process,the increased accreditation and interflow highlighted the role of consensus in forensic standards for forensic service providers to avoid uncertainty regarding the methods used and interpretation of *** 2017,a policy document was promulgated again to strengthen the importance of the uniform standards,which also proposed to establish a new national technical committee for the standardization of forensic science by the General Office of the State *** 2018,despite the continuing problems concerning uniformity,the forensic Administration of the Ministry of Justice was merged into the Public Legal Services ***,there is still a long way to go for the national technical committee for the standardization of forensic *** paper analyses the evolution of forensic standards internationally and nationally,discusses the existing problems,and proposes relative ***,it discusses the future of standards development with the deepening of the reformation of both the national standardization and judicial system.

关键词： forensic sciences standards accreditation technical committee reform

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Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression-and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4801-4822页

作者： Kaikai Zhang Lijian Chen Jianzheng Yang Jiali Liu Jiahao Li Yi Liu Xiuwen Li Long Chen Clare Hsu Jiahao Zeng Xiaoli Xie Qi Wang Guangzhou key laboratory of forensic Multi-Omics for Precision Identification School of Forensic MedicineSouthern Medical UniversityGuangzhou 510515China Department of toxicology School of Public HealthSouthern Medical University(Guangdong Provincial Key Laboratory of Tropical Disease Research)Guangzhou 510515China

Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and *** gut microbiota is a crucial contributor to maintaining host mental ***,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms ***,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the ***-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in ***,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like ***,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of *** activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like *** findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent *** study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.

关键词： Methamphetamine Gut microbiota Short-chain fatty acids Sigma-1 receptor Mental disorders Colonic inflammation Intestinal barrier Gut-brain axis

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