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Pharmacology & Pharmacy 2020年第10期11卷 282-298页

作者： wei-hsi chen Chyng-Yann Shiue Chemistry Division Institute of Nuclear Energy Research Taiwan PET Center Department of Nuclear Medicine National Taiwan University Hospital Taiwan PET Center Department of Nuclear Medicine Tri-Service General Hospital Taiwan

A high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analytical method was developed to determine the identity of impurities resulting from the synthesis of N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzyl-amine (F-ADAM), as well as its metabolic products by rat liver microsomes. 18F-ADAM is an important positive electron emission ligand commonly employed as a radio-imaging agent for serotonin transporter (SERT) in the brain. F-ADAM and its derivatives were separated using HPLC on a C4-phenyl column with an ammonium formate aqueous buffer/acetonitrile programmed mobile phase. Synthetic contaminants and metabolic products were identified using fragmentation spectra obtained by tandem mass spectrometry. We show that F-ADAM is unstable in methanol, and propose the use of acetonitrile to generate optimal chromatogram. A Cl-substituted species was found to be the major impurity resulting from the F-ADAM synthetic process. The metabolic products of F-ADAM by rat liver microsomes were characterized by oxidization of the sulfur moiety to sulfoxide, demethylation of the dimethylamine moiety, and oxidative defluorination/deamination. These results elucidate the by-products of F-ADAM synthetic and metabolic processes, and provide direction for the application of this imaging agent to biosystems properly.

关键词： Liver Microsomes Metabolites Impurities F-ADAM Serotonin Transporter

Sexual Behavior, Function and Satisfaction in Headache Associated with Sexual Activity: A Systematic Review of Literature

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Advances in Sexual Medicine 2017年第2期7卷 65-81页

作者： wei-hsi chen Mei-Yen Chu Yen-Chin Lin Graduate School of Human Sexuality Shu-Te University Taiwan Department of Neurology Kaohsiung Chang Gung Memorial Hospital College of Medicine Chang Gung University Taiwan Life Education Center Chang Jung Senior High School Taiwan

Introduction: Headache associated with sexual activity (HSA) is the painful event of head and neck precipitated only by sexual activity. The negative impact of sexuality is expected to be more severe in HSA patients and their partners than other headache disorder. In addition, social and cultural taboo may conceal sexual problem or hinder seeking counseling for sexual perplexity. A sufficient scientific evidence is therefore needed to clarify the misunderstanding and schedule appropriate education in clinical practice. Methods: A systematic review of literature was completed to elucidate the sexual behavior, function and satisfaction in HSA patients and their partners. Results: A total of 97 publications are eligible after careful screening. However, most of the studies focus on the etiopathogenesis or treatment. Sexual change was mentioned in 23 publications. Orgasmic headache is the most frequent type of HSA. The HSA occurs more frequent in dyadic than extradyadic sexual activity. Intercourse is the leading sexual act for HSA occurrence, following by masturbation. A few patients suffer HSA under specific sexual position, like kneeling, and trigger, such as cannabis. Pain can be rapidly ceased in half of patients when sexual activity was halted. Sexual function and sexual satisfaction may decrease in HSA patient and partner but improve after pain reversal. Conclusions: A shortage of sexuality data of HSA is documented in literature but that still clarifies the extradyadic and masturbatory effect on HSA occurrence. Nevertheless, HSA disturbs sexual function and satisfaction in patients and their partners. The pathogenesis of pain includes two components, the hypersympathetic status and exertional action. Therefore, physician can schedule their education and counseling for HSA according to these findings. Further investigation for sexual function and satisfaction is warranted.

关键词： Headache Sexual Activity Masturbation Intercourse Pain

Current Evidence of the Monoaminergic Regulation of Romantic Love and Relationship

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Advances in Sexual Medicine 2017年第3期7卷 139-152页

作者： wei-hsi chen Mei-Yen Chu Yuan-hsiang Chu Yen-Chin Lin Kuo-Yen chen Graduate School of Human Sexuality Shu-Te University Taiwan Department of Neurology Kaohsiung Chang Gung Memorial Hospital and College of Medicine Chang Gung University Taiwan Life Education Center Chang Jung Senior High School Taiwan

Introduction: Sexual response cycle is modulated by a variety of biological factors, especially antidepressants and antipsychotics. Although the circuit of romantic love has recently been delineated, the biological impact on romantic love is barely mentioned in human, however. Methods: In thus study, a comprehensive literature review was completed to elucidate the role of central monoamines, including dopamine, serotonin, norepinephrine, epinephrine, melatonin and histamine, for the romantic love and relationship in human. Results: The central circuit of romantic love includes the mesolimbic and mesocortical tract and their extensions widely distributed in cortical, subcortical and brainstem structures. The activation of brain foci progressively decreases along with the romantic relationship in many areas, including the bilateral caudate and ventral tegmentum area without change of passionate love. Hyperactivity of dopamine and serotonin is suggested at the synaptic level for romantic love in lovers, probably through an inhibition of transporters or increase of terminal release. Romantic love can be modulated by antidepressants or recreational drugs. Polymorphism of dopamine and serotonin receptor relates to the romantic relationship. The effect of other monoamines is barely mentioned. Conclusions: Romantic love is vulnerable for secondary effect, such as drugs which modulate the dopamine and serotonin, in human. Romantic relationship is also impacted by the polymorphism of monoamine receptors. Therefore, the biological effect is not limited to sexual response cycle but also the romantic love and relationship. Further investigation is warranted for understanding the secondary effect in romantic love for romantic dissolution or divorce.

关键词： Romantic Love Passionate Love Love Dopamine Serotonin

Determination of Impurities and Degradation Products/Causes for <i>m</i>-Iodobenzylguanidine Using HPLC-Tandem Mass Spectrometry

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American Journal of Analytical Chemistry 2019年第11期10卷 590-607页

作者： wei-hsi chen Yu Chang Ching-Yun Lee Shiu-Wen Liu Wen-Ching Wu Tsai-Yueh Luo Chemistry Division Institute of Nuclear Energy Research Taiwan Technology Promotion Center Institute of Nuclear Energy Research Taiwan

m-Iodobenzylguanidinium hemisulfate (MIBGHS) is a precursor in the preparation of radioiodine-labeled m-iodobenzylguanidine (MIBG), which is used as a radio-imaging and therapy agent for neuroendocrine tumors and myocardial sympathetic nerve function. To ensure the quality and efficacy of the medicine and prevent side effects, the precursor purity, source of impurity, and derivatives have to be determined. In this study, the purity of synthesized MIBGHS and the amount of contaminants therein were determined by high-performance liquid chromatography and ultraviolet detection, gradient eluted by ammonium formate aqueous solution and acetonitrile mobile phase on both C8 and phenyl type column. The impurities were identified on the basis of molecular and fragmented ion mass spectra using of electrospray ionization triple quadrupole tandem mass spectrometry. The results revealed the presence of process-related impurities including m-bromobenzylguanidine (MBrBG) and overreacted byproducts. Stress test results indicated that MIBGHS is stable under acidic and dry thermal conditions for at least 72 h but MIBG aqueous solution was deteriorated slowly when exposed to UV light, thermal, oxidative and alkaline environments. Thus, m-iodobenzylamine, the starting material intended for the synthesis of MIBGHS should be analyzed to ensure that it is free from m-bromobenzylamine impurity. Stored under normal condition (-18°C), MIBGHS is stable for at least 12 months. The chemically labile guanidine and amine groups in MIBGHS are the major causes of its instability, while iodide loss from the phenyl group is a minor cause.

关键词： MIBG m-Iodobenzylguanidine Neuroendocrine Tumor Degradation Derivative Impurity Identification Tandem Mass Spectrometry

Determination of Fragmentation Schemes and Metabolites of Fluorinated Histone Deacetylase Inhibitors for Use as Positron Emission Tomography Imaging Agents Using HPLC-MS/MS

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International Journal of Analytical Mass Spectrometry and Chromatography 2018年第1期6卷 1-19页

作者： wei-hsi chen Yu-Chieh hsiao Ming-hsin Li Mu-chen Tsai Chun-Fang Feng Han-Chih Chang Hung-Wen Yu Chyng-Yann Shiue Chemistry Division Institute of Nuclear Energy Research Taiwan Isotope Application Division Institute of Nuclear Energy Research Taiwan PET Center Department of Nuclear Medicine National Taiwan University Hospital Taiwan PET Center Department of Nuclear Medicine Tri-Service General Hospital Taiwan

High performance liquid chromatography coupled with tandem mass spectrometry was developed and validated as a method for the analysis of fluorinated histone deacetylase inhibitors (F-HDACi), and then employed to study their metabolism in biosystems. Four HDACi analogs labeled with the positron emission nuclide 18F constitute a group of potential positron emission tomography imaging agents, which were developed by the Institute of Nuclear Energy Research (INER) and coded as INER-1577 #1, #2, #3, and #4 during animal studies for the diagnosis of dementia. The performance of the method was found to be suitable for the determination of analog #3, and it was employed to determine the structures and fragmentation mechanisms of all four analogs and to study the biotransformations of analogs #3 and #4. The results indicated that the method used for the determination of analog #3 was suitable for determining the abundance of the analogs in chemical and biochemical tests with high precision, accuracy, reproducibility, and recovery. Weaknesses in the chemical bonding of the analogs were found to involve the fluoro, dimethylamino, and benzamide groups in a fragmentation mechanism deduced via tandem mass spectrometry. The metabolites of analogs #3 and #4 in rat liver microsomes and rat plasma were also identified to clarify their characteristic behaviors in biosystems. The major product of analogs #3 in liver microsomes was produced by hydroxylation of the benzylic carbon atom, but in rat plasma the metabolites of analog #3 were produced by hydrolysis of the benzamide group to give a diaminobiphenyl compound with the simultaneous replacement of a fluorine atom by a hydroxyl group. The metabolites of analog #4 in liver microsomes were produced by hydroxylation of the benzylic carbon atom and hydrolysis of the benzamide bond. The results of the studies characterized the chemical and biochemical behaviors of the series F-HADCi analogs.

关键词： Histone Deacetylase Inhibitors Positron Emission Tomography Imaging Agent Dementia LC-Tandem MS Fragmentation Mechanism Metabolism Pathways Epigenetics

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

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Neural Regeneration Research 2025年第1期20卷 159-173页

作者： Man Han Deyang Zeng wei Tan Xingxing chen Shuyuan Bai Qiong Wu Yushan chen Zhen wei Yufei Mei Yan Zeng Brain Science and Advanced Technology Institute Wuhan University of Science and TechnologyWuhanHubei ProvinceChina Geriatric Hospital Affiliated to Wuhan University of Science and Technology WuhanHubei ProvinceChina School of Public Health Wuhan University of Science and TechnologyWuhanHubei ProvinceChina

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral *** studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and *** how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress *** this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of *** focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine *** determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic ***,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

关键词： amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area

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Role of iron ore in enhancing gasification of iron coke:Structural evolution,influence mechanism and kinetic analysis

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 58-69页

作者： Jie Wang wei Wang Xuheng chen Junfang Bao Qiuyue Hao Heng Zheng Runsheng Xu School of Chemistry and Materials Science Hubei Engineering UniversityXiaogan 432000China Key Laboratory for Ferrous Metallurgy and Resources Utilization of Ministry of Education Wuhan University of Science and TechnologyWuhan 430081China Institue of Ironmaking Technology Baosteel Central Research InstituteShanghai 201999China State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

The utilization of iron coke provides a green pathway for low-carbon *** uncover the influence mechanism of iron ore on the behavior and kinetics of iron coke gasification,the effect of iron ore on the microstructure of iron coke was ***,a comparative study of the gasification reactions between iron coke and coke was conducted through non-isothermal thermogravimetric *** findings indicate that compared to coke,iron coke exhibits an augmentation in micropores and specific surface area,and the micropores further extend and *** provides more adsorption sites for CO_(2) molecules during the gasification process,resulting in a reduction in the initial gasification temperature of iron *** the heating rate in non-isothermal gasification can enhance the reactivity of iron *** metallic iron reduced from iron ore is embedded in the carbon matrix,reducing the orderliness of the carbon structure,which is primarily responsible for the heightened reactivity of the carbon *** kinetic study indicates that the random pore model can effectively represent the gasification process of iron coke due to its rich pore ***,as the proportion of iron ore increases,the activation energy for the carbon gasification gradually decreases,from 246.2 kJ/mol for coke to 192.5 kJ/mol for iron coke 15wt%.

关键词： low-carbon ironmaking iron coke gasification structural evolution kinetic model

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Dative B–N bonds weaven toward two-dimensional purely organic materials for single crystals

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Science China Chemistry 2025年第01期 12-14页

作者： wei-Lei Zhou Siwei Wang Yong chen College of Chemistry and Materials Science Inner Mongolia Key Laboratory of Chemistry for Nature Products and Synthesis for Functional Molecules Innovation Team of Optical Functional Molecular Devices Inner Mongolia Minzu University College of Chemistry Nankai University

Molecular topology is one of the important topics to study and understand the relationship between molecular structure and properties [1]. Particularly, two-dimensional (2D) materials with extremely high surface area and ultra-thin morphology have attracted considerable attention due to their unexpected properties in materials and chemistry [2,3].

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Efficient photocatalytic reduction of CO2 to formate by a molecular noble metal-free system

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Science China Chemistry 2025年第1期 152-156页

作者： Lihua Zhang Lingjing chen Huatian Shi Yue wei Gui chen Tai-Chu Lau School of Environment and Civil Engineering Research Center for Eco-environmental Engineering Dongguan University of Technology Department of Chemistry and Institute of Molecular Functional Materials City University of Hong Kong

Reducing CO2to carbon-neutral solar fuels can not only alleviate the energy demand but also mitigate the greenhouse *** present,developing an efficient non-noble metal photo/electrocatalytic system for converting CO2to a specific product beyond CO is still a big ***,we report a new cobalt complex bearing 2,2′-bi-1,10-phenanthroline ligand that can photocatalytically reduce CO2to formate （HCOO-）.Turnover number （TON） for HCOO-up to 677 with 99%selectivity can be achieved using organic dyes purpurin as photosensitizer and 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole （BIH） as sacrificial reductant in a CO2-saturated NMP/TEA （v/v,3:1） solution under visible light *** potential electrolysis at-1.41 V （***/Ag Cl） in the presence of 12 m M Et3NHBF4also produced HCOO-with Faradaic efficiency of 39%.Spectroscopic and electrochemical studies suggest that a[CoI-H]species is the key intermediate for CO2reduction.

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang chen Zhifeng chen Menghua Li weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi wei chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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