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Organic Chemistry Frontiers 2022年第5期9卷 1403-1409页

作者： Yong-Ji Hu Yu Zhou Jing-Jing Gao Han Zhang Kai-Rui yang Jia-Jun Li xiao-xin yan Yuan-Lin Li yan-Ping Zhu School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityShandongYantai264005P.R.China

An I_(2)-mediated[3+2]annulation of methyl-azaarenes with alkyl_(2)-isocyanoacetates or amino acid ester hydrochlorides has been demonstrated.This strategy involves CuN bond cleavage of isocyanides and can selectively synthesize iodine-functionalized and non-iodine-functionalized fused imidazoles.Scale-up experiments and arylation,alkynylation,alkenylation and selenization of iodine-functionalized products demonstrated the potential applications of this reaction.

关键词： reaction iodine fused

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

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Protein & Cell 2022年第1期13卷 26-46页

作者： Weili yang Xiangyu Guo Zhuchi Tu Xiusheng Chen Rui Han yanting Liu Sen yan Qi Wang Zhifu Wang Xianxian Zhao Yunpeng Zhang xin Xiong Huiming yang Peng Yin Huida Wan xingxing Chen Jifeng Guo xiao-xin yan Lujian Liao Shihua Li xiao-Jiang Li Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhou 510632China Key Laboratory of Brain Functional Genomics of Ministry of Education Shanghai Key Laboratory of Brain Functional Genomicsand Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 100021China Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China Department of Anatomy and Neurobiology Xiangya School of MedicineCentral South UniversityChangsha 410008China

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease(PD).However,difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1.Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains.CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology.Importantly,PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival.Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

关键词： Parkinson's disease neurogenesis neurodegeneration mitochondria non-human primates

Cultural Dislocation and Humanity Lost:A Post-Colonial Analysis of Alice Walker’s“Everyday Use”

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Journal of Literature and Art Studies 2023年第8期13卷 580-584页

作者： xiao xin-yan University of Shanghai Science and Technology ShanghaiChina

Alice Walker is a famous African-American female author whose short story“Everyday Use”takes the conflict between a mother and her two daughters over the final ownership of“a quilt”as the main line and creates three black women characters with bright personality.This paper will focus on the living conditions and spiritual world of black women,and reflects the anxiety of black women on ethnic cultural heritage within the white world and reveals the suppression of the strong culture to the weak culture,and the self-preservation of the weak culture from the perspective of post-colonialism.

关键词： “Everyday use” post-colonialism black women cultural dislocation

Metabotropic glutamate receptors(mGluRs)in epileptogenesis:an update on abnormal mGluRs signaling and its therapeutic implications

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Neural Regeneration Research 2024年第2期19卷 360-368页

作者： Leyi Huang Wenjie xiao yan Wang Juan Li Jiaoe Gong Ewen Tu Lili Long Bo xiao xiaoxin yan Lily Wan Department of Anatomy and Neurobiology Central South University Xiangya Medical SchoolChangshaHunan ProvinceChina Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology Hunan Children’s HospitalChangshaHunan ProvinceChina Department of Neurology Brain Hospital of Hunan ProvinceChangshaHunan ProvinceChina

Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

关键词： antiepileptic drugs epileptogenesis metabotropic glutamate receptors(mGluRs) signal pathways therapeutic potentials

Progress in Human Brain Banking in China

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Neuroscience Bulletin 2019年第2期35卷 179-182页

作者： Chao Ma Ai-Min Bao xiao-xin yan Dick F. Swaab Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Department of Human Anatomy Histol-ogy and Embryology Neuroscience Center Joint Laboratory of Anesthesia and Pain School of Basic Medicine Peking Union Medical College Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Institute of Neuroscience NHC and CAMS Key Laboratory of Medical NeurobiologyZhejiang University School of Medicine Department of Anatomy and Neurobiology Central South University School of Basic Medical Science Department Neuropsychiatric Disorders Netherlands Insti-tute for Neuroscience an Institute of the Royal Netherlands Academy of Arts and Sciences

Human brain banks collect,preserve,and distribute postmortem and biopsied brain samples for histological,pathological,and molecular research.Different from the western countries,human brain banking in China has remained preliminary over decades.However,joint efforts during the past few years have substantially promoted this key frontier of neuroscience in China.This special topic brings together review and perspective articles on the ethical,administrative,and practical issues of brain banking.Several original studies report molecular and pathological characterizations based on banked human brain samples.

关键词： collect Progress Banking

Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

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Neural Regeneration Research 2015年第9期10卷 1450-1456页

作者： Xu He Feng-jun Deng Jin-wen Ge xiao-xin yan Ai-hua Pan Zhi-yuan Li Department of Anatomy and Neurobiology School of Basic Medical Sciences Central South University Department of Anatomy Yiyang Medical College Department of Pharmacy Yiyang Medical College Department of Integrated Traditional and Western Medicine Hunan University of Traditional Chinese Medicine

The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginsertg have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa- ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou- blecortin （DCX）＋ neural progenitor ceils and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX＋ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX＋ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.

关键词： nerve regeneration total saponins of Panax notoginseng cerebral ischemia/reperfusion immature neurons neurogenesis doublecortin olfactory bulb neural regeneration

Advances in Alzheimer’s disease (AAD): Standing firm at its first anniversary

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Advances in Alzheimer's Disease 2013年第2期2卷 49-50页

作者： xiao-xin yan Department of Anatomy and Neurobiology Central South University Xiangya School of Medicine Changsha China

Editorial: Advances in Alzheimer’s disease (AAD): Standing firm at its first

关键词： Editorial AAD

Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443

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Chinese Journal of Integrative Medicine 2024年第3期30卷 213-221页

作者： ZHANG Yue xiao yan-wei MA Jing-xin WANG Ao-xue Department of Dermatology the Second Hospital of Dalian Medical UniversityDalianLiaoning Province116021China Department of Cell Biology Dalian Medical UniversityDalianLiaoning Province116044China

Objective:To investigate the effect and possible mechanism of hydroxysafflor yellow A(HSYA) on human immortalized keratinocyte cell proliferation and migration.Methods:HaCaT cells were treated with HSYA.Cell proliferation was detected by the cell counting kit-8 assay,and cell migration was measured using wound healing assay and Transwell migration assay.The mRNA and protein expression levels of heparin-binding epidermal growth factor(EGF)-like growth factor(HBEGF),EGF receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),and hypoxia-inducible factor-1α(HIF-1α) were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot,respectively.Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA.The expression of circ_0084443 was detected by qRT-PCR.Results:HSYA(800 μmol/L) significantly promoted HaCaT cell proliferation and migration(P0.05).Conclusion:HSYA played an accelerative role in HaCaT cell proliferation and migration,which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways,and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

关键词： hydroxysafflor yellow A circ_0084443 heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor phosphatidylinositol 3-kinase/protein kinase B

Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 370-375页

作者： Sheng-yan Liu Lu-Hao Li Zhao-Chen Liu Su-xin Li xiao-Wei Dang Department of Hepatopancreatobiliary Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Budd-Chiari Syndrome Diagnosis and Treatment Center of Henan Province Zhengzhou 450052China

Background:Hepatocellular carcinoma(HCC)is a serious complication of hepatic vena cava Budd-Chiari syndrome(HVC-BCS)that significantly reduces the survival time of patients.Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system.Methods:The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed.Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups.Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical,tumor,and etiological characteristics on the total survival time of patients,and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model.The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index.Results:Multivariate analysis showed that serum albumin level7 cm(HR=8.623,95%CI:3.771-19.715,P<0.001),and inferior vena cava stenosis(HR=3.612,95%CI:1.646-7.928,P=0.001)were independent predictors of survival.A prognostic scoring system was developed according to the above-mentioned independent predictors,and patients were classified into grades A,B,C and D.Significant differences in survival were found among the four groups.Conclusions:This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC,which is helpful for clinical evaluation of patient prognosis.

关键词： Budd-Chiari syndrome Hepatocellular carcinoma Prognostic factors Inferior vena cava stenosis Prognostic scoring system

Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO yan-fang GU Shu-xiao CHAI xin-lou School of Traditional Chinese Medicine Beijing University of Chinese Medicine

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol(LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor(LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9(PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway