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Cyproheptadine Regulates Pyramidal Neuron Excitability in Mouse Medial Prefrontal Cortex

Neuroscience Bulletin 2018年第5期34卷 759-768页

作者： yan-lin He Kai Wang qian-Ru Zhao yan-Ai Mei Institutes of Brain Science State Key Laboratory of Medical Neurobiology and School of Life Sciences Fudan University

Cyproheptadine （CPH）, a first-generation anti- histamine, enhances the delayed rectifier outward K＋ current （IK） in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH （10 μmol/L） significantly reduced the current density required to generate action potentials （APs） and increased the instan- taneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential （RMP）, decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mim- icked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium （TEA） to block IK channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive IK channels as well as other TEA-insensitive K＋ channels, probably ID and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.

关键词： Cyproheptadine Neuronal excitability Te-traethylammonium-sensitive Ik cortical neurons Sigma-1 receptor

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU yan-lin LV lin qian The First Clinical Medical College of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular Department and Gansu Clinical Research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is *** Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction *** Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association *** without myocardial infarction history,HF,or LV ejection fraction(LVEF)ling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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糖尿病肾病模型:动物模型、二维细胞模拟及三维类器官模型

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中国组织工程研究 2025年第17期29卷 3632-3640页

作者：钱足平陈勇冉燕达静静查艳遵义医科大学贵州省遵义市563000 贵州省人民医院肾内科贵州省贵阳市550002

背景:近几年来,人类多能干细胞衍生的肾类器官及糖尿病肾病啮齿动物模型取得了一定的进展。然而,由于糖尿病肾病发病受环境因素及遗传因素共同作用,发病机制复杂,并且对于此类患者的临床治疗方法需要因人而异。因此,需要开发更灵活和综... 详细信息

背景:近几年来,人类多能干细胞衍生的肾类器官及糖尿病肾病啮齿动物模型取得了一定的进展。然而,由于糖尿病肾病发病受环境因素及遗传因素共同作用,发病机制复杂,并且对于此类患者的临床治疗方法需要因人而异。因此,需要开发更灵活和综合的方法,从而发现强有力的临床前证据,以支持对糖尿病肾病患者进行更有针对性的干预。目的:从动物模型、二维细胞培养模拟及三维类器官模型等方面综述了糖尿病肾病模型的研究进展,为进一步的研究提供线索和思路。方法:以“糖尿病,糖尿病肾病,糖尿病肾病模型,糖尿病肾病动物模型,类器官,肾脏类器官,糖尿病肾病细胞模型,糖尿病肾病病证结合动物模型”为中文检索词,“Diabetes,diabetic nephropathy,diabetic kidney diseases,diabetic nephropathy models,diabetic nephropathy animal models,organoids,diabetic and organoids,diabetic and kidney organoids,kidney organoids,diabetic nephropathy cell models,diabetic nephropathy syndrome combined animal models”为英文检索词,检索中国知网及PubMed数据库,最终纳入101篇文献进行综述分析。结果与结论:糖尿病肾病体内模型和体外模型是深入研究糖尿病肾病发病机制的有力工具。动物模型可以观察到多系统之间的相互作用;二维细胞培养操作简便且成本较低;新兴的肾类器官填补了二维和整体水平之间的空白,无种属差异且一定程度模拟了人肾脏的复杂性。随着类器官技术的不断发展,肾类器官有望为探索糖尿病肾病的发病机制、病理生理过程和药物筛选提供一个新的视角。

关键词：糖尿病肾病肾脏类器官糖尿病肾病类器官细胞模型动物模型中医病证结合糖尿病肾病模型工程化组织构建

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A novel squaraine dye with squaramide as a scaffold and the colorimetric detection of amine

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Chinese Chemical Letters 2012年第2期23卷 217-220页

作者： Chuan Guo Sun qian lin Nan yan Fu Key Laboratory of Analysis and Detection for Food Safety Ministry of Education&Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food SafetyCollege of Chemistry and Chemical EngineeringFuzhou UniversityFuzhou 350108China

A novel unsymmetrical squaramide-linked squaraine dye（SQ） has been synthesized through squaramide 3 and semisquaraine 6. The molecular structure of SQ has been characterized by ~1H NMR,IR and *** to the influence of the hydrogen bond and the solvent effect,SQ exhibits unique spectral properties compared with typical squaraine *** its excellent ability of binding primary amine,SQ is a promising receptor of recognizing primary amine.

关键词： Squaraine dye Squaramide Hydrogen bond Receptor

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A simple method for solving unidirectional methane gas flow in coal seam based on similarity solution

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International Journal of Mining Science and Technology 2018年第2期28卷 331-334页

作者： Zhou yan Meng qian lin Baiquan Qin Jilong Zhou Guiping Key Laboratory of Gas and Fire Control for Coal Mines (China University of Mining & Technology) Ministry of Education School of Computer Science and Technology Jiangsu Normal University

The equation used to model the unidirectional flow of methane gas in coal seams is usually formulated as a nonlinear partial differential equation, which needs to be solved numerically with a computer ***, for people without access to the computer program, the conventional numerical method may be inconvenient. Thus, the objective here is to seek some method simpler than the conventional one for solving the flow problem. A commonly used model of the unidirectional methane gas flow is considered, where the methane adsorption is described by the Langmuir isotherm and the free gas is treated as real gas. By introducing the similarity solution, a simple method for solving the flow model is proposed, which can be done on a hand calculator. It is shown by two examples that the gas pressure profile obtained by the proposed method agrees well with the direct numerical solution of the flow model.

关键词： Coalbed methane Migration Unidirectional flow Similarity solution Simplified solving Numerical method

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Evaluating the tumor stratification with a lysosomal pH sensitive-probe by fluorescence lifetime imaging

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Chinese Chemical Letters 2024年第3期35卷 262-267页

作者： Jun yan Xing Liang qian Zhang Luolin Wang Weiying lin Guangxi Key Laboratory of Electrochemical Energy Materials Institute of Optical Materials and Chemical BiologySchool of Chemistry and Chemical EngineeringGuangxi UniversityNanning 530004China

Owing to the anaerobic metabolism in the tumor,abundant acidic metabolites are produced and accumulated in the ***,the cells in different tumor layers are directly linked to the pH ***,due to the lack of robust tools,the high-efficient evaluation of the acidic micro-environment of tumor stratification faces the challenge of accurate *** designed a new pH sensitive fluorescent lifetime probe target to *** we expected,the fluorescence lifetime of PLN possesses a good linear fit to the pH value,which could detect the pH change at a single lysosome level in real time,and then evaluate the different acidity of tumor *** probe PLN is successfully used to evaluate the tumor stratification by fluorescence lifetime imaging microscopy(FLIM)for the first time,which is of great significance in the preoperative diagnosis of clinical tumor treatment or evaluation of drug delivery effect.

关键词： FLIM pH Fluorescence imaging Lysosome Tumor imaging

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2D interspace confined growth of ultrathin MoS_(2)-intercalated graphite hetero-layers for high-rate Li/K storage

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Nano Research 2021年第4期14卷 1061-1068页

作者： yang Li Song Jiang Yong qian Xuedong yan Jie Zhou Zheng Yi Ning lin Yitai qian Department of Applied Chemistry University of Science and Technology ofChinciy Hefei 230026China Hefei National Laboratory for Physical Sciences at the Microscale University of Science and Technology of ChinaHefei 230026China College of Chemical Engineering Ningbo PolytechnicNingbo 315800China Ningbo Veken Battery Co.Ltd Ningbo 315800China

Herein,a two-dimensional(2D)interspace-confined synthetic strategy is developed for producing MoS_(2)intercalated graphite(G-MoS_(2))hetero-layers composite through sulfuring the pre-synthesized stage-1 MoCI5-graphite intercalation compound(M0 CI5-GIC).The in situ grown MoS_(2)nanosheets(3-7 layers)are evenly encapsulated in graphite layers with intimate interface thus forming layer-by-layer MoS_(2)-intercalated graphite *** this structure,the unique merits of MoS_(2)and graphite components are integrated,such as high capacity contribution of MoS_(2)and the flexibility of graphite ***,the tight interfacial interaction between hetero-layers optimizes the potential of conductive graphite layers as matrix for MoS_(2).As a result,the G-MoS_(2)exhibits a high reversible Li+storage of 344 mAh·g^(-1)even at 10 A·g^(-1)and a capacity of 539.9 mAh·g^(-1)after 1,500 cycles at 5 A·g^(-1).As for potassium ion battery,G-MoS_(2)delivers a reversible capacity of 377.0 mAh·g^(-1)at 0.1 A·g^(-1)and 141.2 mAh·g^(-1)even at 2 A·g^(-1).Detailed experiments and density functional theory calculation demonstrate the existence of hetero-layers enhances the diffusion rates of Li^(+)and K^(+).This graphite interspace-confined synthetic methodology would provide new ideas for preparing function-integrated materials in energy storage and conversion,catalysis or other fields.

关键词： interspace-confined MoS_(2)-intercalated graphite hetero-layers Li^(+)storage potassium ion battery

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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu lin Yiming qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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The convergence rate and necessary-and-sufficient condition for the consistency of isogeometric collocation method

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Applied Mathematics(A Journal of Chinese Universities) 2022年第2期37卷 272-289页

作者： lin Hong-wei XIONG Yun-yang HU Hui yan Jia-cong HU qian-qian School of Mathematical Science Zhejiang UniversityHangzhou 310027China Department of Mathematics Zhejiang Gongshang UniversityHangzhou 310018China

Although the isogeometric collocation(IGA-C)method has been successfully utilized in practical applications due to its simplicity and efficiency,only a little theoretical results have been established on the numerical analysis of the IGA-C *** this paper,we deduce the convergence rate of the consistency of the IGA-C ***,based on the formula of the convergence rate,the necessary and sufficient condition for the consistency of the IGA-C method is *** results advance the numerical analysis of the IGA-C method.

关键词： isogeometric collocation consistency necessary and sufficient condition convergence rate

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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China Life Sciences 2025年第1期 204-218页

作者： Chen Xiong Hong ling Yingdan Huang Hanzhi Dong Bangxiang Xie qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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