Biomarkers in the early period of acute myocardial infarction in rat serum and

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生物专业英语第六章生命的起源

生物学定义：当两性分子如磷脂和鞘脂分散于水相时，分子的疏水尾部倾向于聚集在一起，避开水相，而亲水头部暴露在水相，形成具有双分子层结构的的封闭囊泡，称为脂质体。
18. ozone layer n. 臭氧层
[ 'əuzəune atmosphere, about 20 to 50 km above the surface, which contains ozone produced by ultraviolet radiation.
起源的时间
科学回答生命起源的时间--- 化石迄今为止，我们发现了最古老的生物化石是来自澳大利亚西部，距今约三十五亿年前的岩石，这些化石类似于现在的蓝藻，它们是一些原始的生命，是肉眼看不见的。它的大小只有几个微米，到几十个微米。同时我们知道地球的形成年龄大约在46亿年前，这两个数据我们就可以看到生命起源的年龄，大致可以界定在46亿年到35亿年之间。
Words and phrases
1.Big Bang
n. 大爆炸
宇宙大爆炸(Big Bang)
大约在150亿年前，宇宙所有的物质都高度密集在一点，有着极高的温度，因而发生了巨大的爆炸。大爆炸以后，物质开始向外大膨胀，就形成了今天我们看到的宇宙。在这150亿年中先后诞生了星系团、星系、我们的银河系、恒星、太阳系、行星、卫星等。人类就是在这一宇宙演变中诞生的。
生命起源的几种假说
创世说--《圣经》上说，"起初，神创造天地"。自生论--生命是从无生命物质自然发生的。如希腊人认为，昆虫生于土壤，春天万象更新，种子从泥土里萌发，昆虫从去年留下的卵壳中破壳而出。还有比如说埃及人认为生命来自于尼罗河，在中国古代也有腐草生萤之说。宇宙生命论--提倡“一切生命来自宇宙”观点，认为地球上最初的生命来自宇宙间的其他星球，即“地上生命，天外飞来”。这一假说认为，宇宙太空中的“生命胚种”可以随着陨石或其他途径跌落在地球表面，即成为最初的生命起点。

关于海马体的英语阅读理解

关于海马体的英语阅读理解Antidepressant(抗忧郁) drugs such as Prozac were viewed in the early 1900's as wonder pills that would remove depressive blues for good. But in the past five years, growing scientific evidence has shown these drugs work for only a minority of people. And now a research journal says that these antidepressants can make many patients' depression worse. This alarming suggestion centres on the very chemical that is targeted by antidepressants-- serotonin(血清素). Drugs such as Prozac are known as selective serotonin re-uptake inhibitors (or SSRIs) . Their aim is to increase the level of this "feel- good" chemical in the brain. chemical Swiss Army knife, performing a very wide range of jobs in the brain and body. And when we start changing serotonin levels purposely, it may cause a wide range of unwanted effects. These can include digestive problems and even early deaths in older people, according to the study's lead researcher Paul Andrews. "We need to be much more cautious about use of these drugs," says Andrews.Previous research has suggested that the drugs provide ltte benefit for most people with mild depression, and actively help only a few of the most severely depressed. Famous psychologist Irving Kirsch has found that for many patients, SSRIs are no more effective than a placebo pill. A research in 2010 on Danish children found a smal, but significant increase in the risk of heart problems among babies whose mothers had used SSRls in early pregnancy(怀孕). The key to understanding these side-effects is serotonin, says Andrews. Serotonin is also the reason why patients can often end up feeling still more depressed after they have finished a course of SSRI drugs. He argues that SSRI antidepressants disturb the brain, leaving the patient an even greater depression than before.Stafford Light man, professor of medicine at the University of Bristol, and a leading UK expert in brain chemicals and hormones, says Andrews' review highlights some important problems, yet it should also be taken with a pinch of salt. "This report is doing the opposite of what drug companies do," he says. "Drug companies selectively present all thepositives in their research, while this search selectively presents all the negatives that can be found. Nevertheless, Andrews' study is useful in that it is always worth pointing out that there is a downside to any medicine." Professor Lightman adds that there is still a great deal we don't know about SSRIs-- not least what they actually do in our brains.When it comes to understanding why the drugs work only for a limited part of patients, U.S. scientists think they might now have the answer. They think that in many depressed patients, its not only the lack of feel-good serotonin causing their depression, but also a failure in the area of the brain that produces new cells throughout our lives. This area, the hippocampus(海马体) , is also responsible for regulating mood and memory. Research suggests that in patients whose hippocampus has lost the ability to produce new cells, SSRIs do not bring any benefit.1. By saying "serotonin is like a chemical Swiss Army knife" in paragraph 2, the author means that serotonin can_A. make many patients' depression worseB. cause a wide range of unwanted effectsC. affect human body and brain in various waysD. provide little benefit for most depressed people2. In Stafford Light man's opinion,A. Andrews' research has no medical valueB. scientists have found what SSRIs do in the brainC. drug companies don't know the negative effect of antidepressantsD. Andrews and the drug companies focused on different things about the drugs3. Which of the fllowing is TRUE about SSRIs?_A. They are responsible for contrlling mood and memory.B. They create a risk of heart problems in pregnant women.C. They are used to increase the "feel-good" medical in the brain.D. They can work even if the hippocampus can't produce new cells.4. What is the passage mainly about?_A. The aims of drug companiesB. The functions of SSRIsC. The side-effects of antidepressantsD. The causes of depression。

4月15日新托福阅读题解析：讨论最早历法

4月15日新托福阅读题解析：讨论最早历法为了帮助大家备考托福阅读，下面小编给大家带来4月15日新托福阅读题解析：讨论最早历法，希望对大家有所帮助!4月15日新托福阅读题解析：讨论最早历法学科分类：考古类题目：Debate about the earliest calendars内容回忆版本一：第一段：一个考古学家认为骨头上的14个marks 是古代人们记录lunar year的方法，因为它们的排列不是by chance的，而是按照group patterns排列的[有目的题，问作者为什么提到这些具体的pattern, 答案为为了说明这些pattern不是natural(对应not by chance)的，而是人为的]，该学家认为这种pattern和月亮从crescent(新月)到full moon，再从full moon到new moon的时间段一致(有题，问这个考古学家是如何理解上述pattern的，答：和moon的各种phase相符)。

第一段是不是森破?第二段：讲这种日历的用途：古代人推算一些event的period;找到事情的sequencially connected;最终导致writing的出现[并列结构出现，有EXCEPT题]。

虽然最长的pattern只有two and a half months, but多个连接起来可以推算时间的period，如怀孕，洪水的时间[有句子简化题，注意转折逻辑即可]。

第三段：发现我们的祖先可以think abstractly，具有计算日子的能力是件很有意思的事[有事实信息题]，但是也有质疑，因为hunter-gather的祖先了解所有打猎，采集等periodically的时间，不需要记录。

第四段：继续批判第一段中考古学家的观点，说那些marks的pattern是not regular，他也没有provide no example，还没有evidence[一句话中并列结构，有EXCEPT题]。

全身运动不安运动阶段质量评估对婴幼儿神经系统疾病预测价值的Meta分析

全身运动不安运动阶段质量评估对婴幼儿神经系统疾病预测价值的Meta分析门光国;王凤敏;崔英波【摘要】目的探讨婴幼儿早期(出生后20周内)全身运动(GMs)不安运动阶段质量评估对婴幼儿神经系统疾病的预测价值.方法利用数据库检索到2015年12月前发表的相关文献,共有16篇文献纳入研究并进行Meta分析.结果 16篇文献QUADAS评分≥10的有8篇,临床特征等信息差异均无统计学意义(P＞0.05).GMs 不安运动阶段质量评估对神经系统发育不良结局(包括脑性瘫痪)的预测分析显示,灵敏度、特异度、阳性似然比(PLR)、阴性似然比(NLR)和诊断比值比(DOR)分别为0.78、0.93、11.26、0.24和55.43;SROC曲线表明灵敏度和特异度最佳结合点的Q值为0.852 2,AUC值为0.919 0.GMs不安运动阶段质量评估对脑性瘫痪的预测分析显示,灵敏度、特异度、PLR、NLR和DOR分别为0.91、0.94、12.91、0.12和133.66,SROC曲线表明灵敏度和特异度最佳结合点的Q值为0.918 5,AUC值为0.969 2.结论 GMs不安运动阶段质量评估是预测婴幼儿神经系统疾病的一种有效方法,但不推荐单独使用.【期刊名称】《浙江医学》【年(卷),期】2016(038)014【总页数】5页(P1161-1165)【关键词】全身运动;不安运动阶段;婴幼儿;神经系统疾病;脑性瘫痪;Meta分析【作者】门光国;王凤敏;崔英波【作者单位】315012 宁波市妇女儿童医院新生儿科;315012 宁波市妇女儿童医院新生儿科;315012 宁波市妇女儿童医院新生儿科【正文语种】中文全身运动（general movements，GMs）是一种复杂的动作，包括头部、躯干、手臂和腿的运动，出现于胎儿早期并持续到出生后3～4个月。

近年来，GMs质量评估对婴幼儿脑性瘫痪（CP）等神经系统疾病的预测价值得到越来越多证据支持[1-2]。

大学生物专业英语lesson_five

Chargaff´s（查伽夫，美国生物化学家）法则：（1）在DNA中腺嘌呤与胸腺嘧啶含量相等的，胞嘧啶与鸟嘌呤含量相等；（2）腺嘌呤胸腺嘧啶比例和胞嘧啶鸟嘌呤比例随物种不同而不同。
3 The Research race for
the Molecular structure of DNA
In the late 1940s and early 1950s, researchers looking for the structure of DNA drew upon Chargaff's insight, Levene´s ideas on DNA components, and two other lines of evidence.
Nuclei acid, originally isolated by Johann Miescher in 1871, was identified as prime constituent of chromosomes through the use of the red-staining method developed by Feulgen in the early 1900s.
他们的工作为其他研究者精确阐明 “酶是如何影响复杂新陈代谢途径”铺平了道路。
粗糙脉孢菌作为木质纤维素降解真菌，不仅具有完整的木质纤维素降解酶系，而且还拥有全基因组基因敲除突变体库，是研究丝状真菌纤维素酶表达分泌和木质纤维素降解机制的优秀体系。
国内外利用粗糙脉孢菌系统，在木质纤维素降解机制方面取得了显著进展，包括纤维素酶信号传导、调控以及生物质降解后糖的转运利用等。 2019/11/27
Thirty years later Beadle and Ephrussi showed a relationship between particular genes and biosynthetic reactions responsible for eye color in fruit flies.

【每周一练】比促智药更好用的是翻译！

【每周一练】比促智药更好用的是翻译！9月份推出“每周一练”以来，获得了译品译味忠实粉丝的好评，有不少学员坚持参与了每一期的练习。

本月响应大家的要求，推出月卡和季卡，具体见文末。

下面先来看看第四期的点评。

英译汉篇【原文】The COSMOS Standard establishes common requirements and definitions for organic and/or natural cosmetics, and has been developed at the European and international level by BDIH (Germany), COSMEBIO & ECOCERT (France), ICEA (Italy) and SOIL ASSOCIATION (UK).①They are the founders of the COSMOS-standard AISBL, an international non-profit association registered in Belgium.COSMOS validation requires an ingredient to meet criteria defining it as natural in origin and processing. Among the criteria, ingredients must be free of contaminants including pesticides, GMOs, heavy metals, aromatic hydrocarbons, nitrates, nitrosamines, mycotoxins, radioactivity, medicinal residues,dioxins and PCBs above naturally-occurring levels.②The following meet the COSMOS definition of natural origin: physically processed agro-ingredients and chemically processed agro-ingredients derived from plant, animal and microbial sources providing that they meet the COSMOS standard conditions③; water; as well as minerals and ingredients of mineral origin listed in Appendix IV of the COSMOS standard. Chemically processed agro-ingredients may contain petrochemical moieties.（来源：某化学品公司可持续发展报告）【解析】这次重点解析三个出问题较多的句子，涉及对原文理解、逻辑、常识、中文表达习惯等问题。

药学英语Unit 6 Text A 注释及译文

Drug Discovery and Natural Products It may be argued that drug discovery is a recent concept that evolved from modern science during the 20th century, but this concept in reality dates back many centuries, and has its origins in nature. On many occasions, humans have turned to Mother Nature for cures, and discovered unique drug molecules. Thus, the term natural product has become almost synonymous with the concept of drug discovery. In modem drug discovery and development processes, natural products play an important role at the early stage of "lead" discovery, i.e. discovery of the active (determined by various bioassays) natural molecule, which itself or its structural analogues could be an ideal drug candidate.1.origin ['ɔridʒin] n.起点，端点; 来源；出身, 血统.2.Synonymous [sɪ'nɔnəməs]adj.同义的，类义的.3.i.e. [,aɪ'i:] <拉> abbr. (=id est) 即，换言之.4.candidate ['kændidit] n.申请求职者, 候选人；报考者；候选物.有人可能认为药物发现是一个20世纪才出现的、来源于现代科学的新概念，但是事实上这个概念是源于自然界的，可以追溯到许多个世纪以前。

生物化学的发现英文

生物化学的发现英文In the realm of biochemistry, the discovery of DNA's double helix structure stands as a monumental breakthrough.It revolutionized our understanding of genetic informationand paved the way for modern molecular biology.The intricate dance of enzymes and substrates, orchestrating the metabolic pathways within cells, is amarvel of nature's design. Each enzyme, with its unique shape, ensures the specificity and efficiency of biochemical reactions.Another significant revelation in biochemistry is therole of amino acids in protein synthesis. The sequence ofthese building blocks determines the structure and functionof proteins, which are the workhorses of the biological world.The exploration of lipid bilayers and their role in cell membranes has deepened our comprehension of how cellsmaintain their integrity and selectively interact with their environment.The study of biochemistry also unveils the mysteries of cellular energy production. The citric acid cycle andoxidative phosphorylation are processes that convertnutrients into the energy currency of the cell, ATP.Understanding the molecular mechanisms of disease hasbeen greatly advanced by biochemistry. For instance, the identification of the molecular basis of cystic fibrosis has led to more targeted and effective therapies.The emerging field of epigenetics, where biochemistry intersects with genetics, has shed light on how environmental factors can influence gene expression without altering the DNA sequence itself.Finally, the ongoing quest to decode the human proteomeis a testament to the vastness of biochemical knowledge. Each protein's unique function contributes to the symphony of life, and understanding them is key to unlocking the mysteries of health and disease.。

细胞生物学发展史上的故事

细胞生物学发展史上的故事细胞是微小的，细胞生物学所面对的第一个实际问题是如何才能看见细胞。

在17世纪，显微镜的发明第一次是细胞成为可见的物体。

以后几百年内关于细胞的一切知识都是用这种简单装置发现的。

光学显微镜的发展依赖玻璃透镜制造技术的改进。

1665年Robert Hooke 向伦敦皇家学会报告他曾经观察一片软木，发现它由大量小腔室组成，他称这些腔室为“cells”。

“cell”这个名词沿用至今。

细胞的发现得益于光学显微镜的研制和发展。

第一台显微镜是荷兰眼镜商詹森(Hans Janssen)在1604年发明的。

■ 1665年，英国的物理学家胡克用自己设计并制造的显微镜观察栎树软木塞切片时发现其中有许多小室，状如蜂窝，称为"cella"，这是人类第一次发现细胞，不过，胡克发现的只是死的细胞壁(图1-1)。

胡克的发现对细胞学的建立和发展具有开创性的意义，其后，生物学家就用"cell"一词来描述生物体的基本结构。

■ 1674年，荷兰布商列文虎克(Anton van Leeuwenhoek)为了检查布的质量，亲自磨制透镜，装配了高倍显微镜(300倍左右)，并观察到了血细胞、池塘水滴中的原生动物、人类和哺乳类动物的精子，这是人类第一次观察到完整的活细胞。

列文虎克把他的观察结果写信报告给了英国皇家学会，得到英国皇家学会的充分肯定，并很快成为世界知名人士。

谁首先发现了细胞，罗伯特·虎克还是列文虎克？约有200年，直到19世纪，光学显微镜才开始广泛用来考察活细胞。

细胞生物学明确作为一门学科出现是一个渐进的过程，许多人为此做出了贡献。

最早认识到活细胞各结构作用的是Rudolf Brown。

他研究兰科和萝摩科植物细胞，发现了细胞核。

Rudolf Brown于1833年指出，细胞核是植物细胞的重要调节部分。

德国植物学家Matthias Schleiden于1838年发表了著名论文“论植物的发生”，指出细胞是一切植物结构的基本单位。

外刊阅读练习：生物学和金融界的不稳定性

最牛英语口语培训模式：躺在家里练口语，全程外教一对一，三个月畅谈无阻！洛基英语，免费体验全部在线一对一课程：/ielts/xd.html（报名网址）Biology and financial instability生物学和金融界的不稳定性The molecules of mayhem混乱的分子The Hour Between Dog and Wolf: Risk-Taking, Gut Feelings and the Biology of Boom and Bust. By John Coates.狗和狼之间的那一刻：冒险、直觉和繁荣与萧条的生物学。

由约翰·科茨。

The financial crisis was caused by many things: greedy bankers, a glut of Chinese savings,shoddy regulation, an obsession with home ownership—take your pick. John Coates, once a trader on Wall Street and now a neuroscientist at Cambridge University, presents yet another culprit: biology, or, more precisely, the physiology of risk-taking. Financial traders, he says, are influenced by what is going on in their bodies as well as in the markets. Two steroid hormones—testosterone and cortisol—come out in force during the excesses of bull and bear markets.导致金融危机的因素有好几个：贪婪的银行家、中国的大笔储蓄、具误导性的监管制度、对拥屋的痴迷——任你挑选。

关于路易斯巴斯德的英语作文

关于路易斯巴斯德的英语作文Louis Pasteur: The Remarkable Life and Achievements of a Scientific VisionaryLouis Pasteur was a French scientist whose groundbreaking discoveries and innovations revolutionized the field of microbiology and had a profound impact on various aspects of human life. Born in 1822 in the small town of Dole, France, Pasteur's journey from a humble beginning to becoming one of the most influential figures in the history of science is a testament to his unwavering dedication, intellectual curiosity, and relentless pursuit of scientific truth.Pasteur's early life was marked by a strong interest in the natural world and a desire to understand the underlying mechanisms that govern the physical and biological phenomena around him. After completi ng his education at the École Normale Supérieure in Paris, he embarked on a career that would forever change the course of scientific history.One of Pasteur's most significant contributions was his work on the germ theory of disease. At a time when the prevailing belief was that diseases were caused by miasmas or "bad air," Pasteur's researchdemonstrated that many infectious diseases were actually caused by the presence of microscopic organisms, known as microbes or bacteria. This revolutionary idea challenged the established medical practices of the time and paved the way for the development of modern microbiology and epidemiology.Pasteur's groundbreaking experiments, such as his studies on the fermentation of alcohol and the souring of milk, provided clear evidence that these processes were the result of the activities of specific microorganisms. He also made important discoveries in the field of immunology, developing vaccines for several deadly diseases, including rabies, anthrax, and cholera.The impact of Pasteur's work on public health cannot be overstated. His discoveries led to the development of pasteurization, a process of heating liquids to kill harmful bacteria, which has saved countless lives by preventing the spread of foodborne illnesses. Pasteur's work also laid the foundation for the modern pharmaceutical industry, as his research on the role of microorganisms in disease helped pave the way for the development of effective antimicrobial treatments.Beyond his scientific achievements, Pasteur was also a skilled communicator and a passionate advocate for the importance of scientific research. He tirelessly worked to promote the value of scientific inquiry and to educate the public on the significance of hisdiscoveries. Pasteur's eloquence and persuasive power were instrumental in securing funding and support for his research, as well as in convincing the scientific community and the general public to embrace his revolutionary ideas.Pasteur's legacy extends far beyond his scientific accomplishments. He was a man of great integrity and moral character, who believed that science should be used to benefit humanity. Throughout his career, he remained steadfast in his commitment to the pursuit of truth and the betterment of the human condition. His unwavering dedication and his ability to overcome setbacks and challenges serve as an inspiration to scientists and thinkers of all generations.The life and work of Louis Pasteur stand as a shining example of the transformative power of scientific inquiry and the profound impact that a single individual can have on the course of human history. His contributions to the understanding of microbiology, immunology, and public health have had a lasting and far-reaching impact, and his legacy continues to inspire and guide the scientific community and the world at large.。

阿尔茨海默症核心生物标志物及其他生物标志物研究进展

· 45 ·殷宏艳尤斯涵郭春燕河北北方学院药学院，河北省神经药理学重点实验室，张家口，075000，中国【摘要】阿尔茨海默症（Alzheimer's disease ， AD ）是一种神经退行性疾病，至今为止不能治愈。

现存的主要诊断方法是脑脊液中生物标志物的检测以及正电子发射式计算机断层扫描（positron emission computed tomography ， PET ），但由于其测试的侵入性和高成本，阻碍了临床实践中的应用。

血液样本生物标志物由于其易得，价廉的特点，有望可以实现AD 的早期诊断。

该文总结了目前AD 常见的几种生物标志物以及它们在AD 患者中的变化，并对未来AD 生物标志物的发展进行展望。

【关键词】阿尔茨海默症；生物标志物；脑脊液；血液【中图分类号】 R964 【文献标识码】 A DOI ：10.3969/j.issn.2095-1396.2023.06.009Research Progress of Core Markers and Other Markers of Alzheimer's DiseaseYIN Hong-yan ， YOU Si-han ， GUO Chun-yanDepartment of Pharmacy ， Hebei North University ， Hebei Key Laboratory of Neuropharmacology ， Zhangjiakou ， 075000， China【ABSTRACT 】 Alzheimer's disease （AD ） is a neurodegenerative disease that cannot be cured until now. The main existing diagnostic methods are the detection of biomarkers in cerebrospinal fluid and positron emission tomography （PET ）， but their application in clinical practice is hampered due to the invasiveness and high cost of their testing. Biomarkers in blood samples can make early detection and diagnosis of ad universal because of their easy availability and low price. This article summarizes several common biomarkers of AD and their changes in AD patients ， and prospects the development of ad biomarkers in the future.【KEY WORDS 】 Alzheimer's disease ； biomarkers ； cerebrospinal fluid ；blood 阿尔茨海默症核心生物标志物及其他生物标志物研究进展作者简介：殷宏艳，研究方向：药物分析；E-mail ：*****************通讯作者：郭春燕，教授，硕士生导师；研究方向：体内药物分析和靶向药物分析；E-mail ：******************阿尔茨海默症（Alzheimer's disease ， AD ）是一种渐行性神经退行性疾病，是痴呆的主要原因，首次于1906年由Alois Alzheimer 提出［1］。

托福双语阅读素材：再生医学器官真相

托福双语阅读素材：再生医学器官真相想要提高托福阅读力量，我们确定要在日常生活中有意识地增加英语阅读量，提升语感和娴熟度，这其中比较常用也比较便利地一个方式就是利用各类英文报刊杂志文章进展精读与泛读练习。

下面我们来看一篇经济学人文章：再生医学-器官真相。

Regenerative medicineA tissue of truthsThe routine printing of human body parts may not be far away再生医学器官真相在不远的将来，打印人体组织或许会成为常规EVERY year about 120,000 organs, mostly kidneys, are transplanted from one human being to another. Sometimes the donor is a living volunteer. Usually, though, he or she is the victim of an accident, stroke, heart attack or similar sudden event that has terminated the life of an otherwise healthy individual. But a lack of suitable donors, particularly as cars get safer and first-aid becomes more effective, means the supply of such organs is limited. Many people therefore die waiting for a transplant. That has led researchers to study the question of how to build organs from scratch.每年约有12万个器官(主要是肾脏)从一个人身上移植到另一个人身上。

生物制药专业英语天津农学院期末考试翻译范围及答案

Among many early races在很多早期历史中，疾病被认为是恶魔或邪灵进入体内而引起的。

治疗方法相当自然，包括使身体摆脱超自然侵入者。

从历史的最早记录中得出证据，治疗这些疾病的主要方法是通过使用宗教咒语，使用有害物质和特殊中药或植物的使用。

在早期的种族之间，疾病被认为是由恶魔的入侵或者罪恶的灵魂进入体内所引起的。

治疗自然的包括驱除体内的超自然入侵者。

从最早的历史记录开始被证实治疗疾病的主要途径是通过宗教咒语的使用，有害物质的使用和特殊中药或植物的给药。

Before the days of the priestraft在剂师出现之前，那些通过经验或通过口传的关于植物的治愈知识已经被部落的聪明的男人或女人收集起来，他们被召唤来照料那些生病的或受伤的人，并且准备治疗。

这就是在药物的制备中药剂师的技能起源了。

在药剂师出现之前，部落里聪明的人，他们懂得关于植物的治疗特性的知识，这些知识是通过经验或是口口相传下来而收集的。

他们被召集去处理生病或受伤的人并准备治疗法。

在药用材料的准备过程中药剂师这一行业就诞生了。

As time passed随着时间推移，药剂师的角色开始与祭司的功能相结合，并且在早期的文明中术士或医生开始成为身体的治疗者也是灵魂的治疗者。

在他们早期的历史中制药和药物是不能辨别的，因为他们的实践大体是部落宗教领导者的职责。

随着时间推移，药剂师的角色开始与祭司的功能相结合，并且在早期的文明中术士或医生开始成为身体的治疗者也是灵魂的治疗者。

在他们早期的历史中制药和药物是不能辨别的，因为他们的实践大体是部落宗教领导者的职责。

Due to thepatience and由于考古学家的耐心和理解，药物的类别和特殊药物的使用在药物治疗的早期历史中被运用不像猜想中那样难确定。

许多追溯到公元前3000年的古代石碑，卷轴和其他遗物已经被发现和被考古学者解读，这点亮了医药学的历史。

在这些古代文件中与我们传统有特殊的联系。

疯狂英语听力下载：遗传学之父

英语听⼒频道为⼤家整理的疯狂英语听⼒下载：遗传学之⽗，供⼤家参考:)4. Father of Genetics 遗传学之⽗His name is introduced to biology students, but often forgotten after the final exam. His pioneering discoveries went unnoticed by the world until years after his death. But now, in the era of genetic engineering and cloning debates, scientists are elevating Johann Gregor Mendel to his rightful place in history alongside better known, 19th century contemporaries such as Charles Darwin.他的名字常常被介绍给⽣物系的学⽣，但在期末考试后⼜往往被遗忘。

他的发现具有开拓精神，但在他⽣前却⼀直不为世⼈所重视。

不过现如今，在基因⼯程领域和克隆研讨会场合上，科学家们正在将约翰•格雷⼽尔•孟德尔提升到⼀个他应有的历史地位，并列于查尔斯•达尔⽂等19世纪同时代的其他的科学家。

Experts and scientists have collected artwork and artifacts inside the partially restored Abbey of St. Thomas in Brno, a Czech city where Mendel lived, experimented with pea plants and published his historic findings in 1866, becoming the “father of genetics”.专家和科学家们已经从⼀座部分被修复了的捷克布尔诺市圣托马斯修道院中，收集了⼀些艺术品和史前古器物。

衰老生物标志物

衰老生物标志物下载温馨提示:该文档是我店铺精心编制而成，希望大家下载以后，能够帮助大家解决实际的问题。

文档下载后可定制随意修改，请根据实际需要进行相应的调整和使用，谢谢!并且，本店铺为大家提供各种各样类型的实用资料，如教育随笔、日记赏析、句子摘抄、古诗大全、经典美文、话题作文、工作总结、词语解析、文案摘录、其他资料等等，如想了解不同资料格式和写法，敬请关注!Download tips: This document is carefully compiled by theeditor.I hope that after you download them,they can help yousolve practical problems. The document can be customized andmodified after downloading,please adjust and use it according toactual needs, thank you!In addition, our shop provides you with various types ofpractical materials,such as educational essays, diaryappreciation,sentence excerpts,ancient poems,classic articles,topic composition,work summary,word parsing,copy excerpts,other materials and so on,want to know different data formats andwriting methods,please pay attention!探索衰老的生物标志物：揭示生命时钟的秘密衰老，是生命过程中不可避免的现象，其内在机制复杂且多元。

疫苗的来历英语科普作文

疫苗的来历英语科普作文Title: The Origin of Vaccines: A Comprehensive Exploration。

Introduction:Vaccines, a cornerstone of modern medicine, have revolutionized public health by preventing countless diseases. However, their history is not widely known. This essay delves into the fascinating origins of vaccines, tracing their journey from ancient practices to modern scientific breakthroughs.Ancient Practices:The concept of immunization dates back thousands of years. Ancient civilizations, including the Chinese, Indians, and Egyptians, practiced variolation, a method where individuals were exposed to smallpox scabs or pus to induce immunity. While crude by today's standards, thisprimitive form of vaccination laid the groundwork forfuture developments.The Age of Enlightenment:The 18th century marked a turning point with the advent of inoculation in Europe. Lady Mary Wortley Montagu, influenced by her experiences in the Ottoman Empire, introduced smallpox inoculation to England after witnessing its effectiveness. However, this method still carried risks and was far from perfect.The Discovery of Vaccination:The true breakthrough came in the late 18th century with the pioneering work of Edward Jenner, an English physician. Jenner observed that milkmaids who contracted cowpox, a mild disease similar to smallpox, appeared immune to smallpox. Building on this observation, Jenner performed the world's first vaccination experiment in 1796, successfully protecting a young boy from smallpox using cowpox material.The Rise of Modern Vaccinology:Jenner's discovery laid the foundation for modern vaccinology. Throughout the 19th and 20th centuries, scientists refined vaccination techniques and developed vaccines against various diseases, including rabies, cholera, and tetanus. The landmark discovery of Louis Pasteur, who developed the first attenuated vaccine for chicken cholera in 1879, further propelled vaccine research.The Golden Age of Vaccines:The 20th century witnessed unprecedented progress in vaccine development. The introduction of vaccines for diseases like polio, measles, mumps, and rubella led to dramatic declines in morbidity and mortality worldwide. Mass vaccination campaigns, supported by advancements in manufacturing and distribution, played a pivotal role in eradicating smallpox and nearly eliminating diseases like polio.Challenges and Controversies:Despite their undeniable benefits, vaccines have faced opposition and controversy throughout history. Misinformation, fear of side effects, and distrust in medical authorities have fueled vaccine hesitancy, leading to outbreaks of preventable diseases. Addressing these challenges remains critical in ensuring widespread vaccine acceptance and maintaining herd immunity.The Future of Vaccines:Looking ahead, vaccines continue to hold immense promise. Advances in biotechnology, including the development of mRNA vaccines, offer new avenues for combating infectious diseases and even certain cancers. Moreover, the COVID-19 pandemic has underscored the urgency of vaccine research and global cooperation in addressing emerging threats.Conclusion:In conclusion, vaccines represent one of humanity's greatest achievements in public health. From ancient practices to modern science, the journey of vaccines reflects centuries of innovation, perseverance, and collaboration. As we navigate the challenges of the 21st century, vaccines remain indispensable tools in safeguarding global health and ensuring a brighter future for generations to come.。

托福阅读真题词汇 TPO 2

TPO2
The origin of cetaceans
cetacean
鲸类
fluke
尾片
disguise
伪装
sea otter walrus
海獭海象
bridge
连接
precious
珍贵的
flesh-eating
吃肉的
scarce
缺乏的
initiate expose
开始暴露
marine
海洋的
locomotion
粪结果的
模式装置营业室模型，模仿留声机简单地合法的，合理的最终的壮观的，精彩的集合，装配参与常见的事物来临，到来二十，配乐极小的原型

后腿气孔密切关系鳍足类想象头骨探测浅的起初的繁殖，品种退化的，残余的沉淀物脊椎漂着的骨骼，骨架
十年威胁限制保持颗粒穿透，渗透减少完成加速吸收 absorb 边界受制于，易遭受页边，边缘渐进地，日益增多地一块土地易受影响的盐度壳的干涉，妨碍不足的逆转；相反的相当大的实施，执行
livestock subsequent seal
Early cinema emerge project devise successive roughly exhibitor admission approval spectacle spectator previously marvel manipulate with the advent of expand dimension acquire
牲畜随后的密封；印章；海豹
dung consequent
出现投影；预计；项目设计，发明连续的粗糙的，粗略的电影放映商允许同意，赞成 approve 场面，景象，奇观观众先前地奇迹操纵随着…的到来扩张维度得到

2021年3月15日GRE阅读机经

2021年3月15日GRE阅读机经Reading Comprehension Although passenger pigeons, now extinct, were abundant in eighteenth-and nineteenth-century America, archaeological studies at twelfth-century Cahokian sites in the present-day United States examined household food trash and found that traces of passenger pigeon were quite rare. Given that the sites were close to a huge passenger pigeon roost documented by John James Audubon in the nineteenth century and that Cahokians consumed almost every other animal protein source available, the archaeologist conducting the studies concluded the passenger pigeon population had once been very limited before increasing dramatically in post-Columbian America. Other archaeologists have criticized those conclusions on the grounds that passenger pigeon bones would not be likely to be preserved. But all the archaeological projects found plenty of bird bones--and even some tiny bones from fish.7. The author of the passage mentions "tiny bones from fish" primarily in order to A. Explain why traces of passenger pigeon are rare at Cahokian sites B. Support a claim about the wide variety of animal proteins in the Cahokian diet C. Provide evidence that confirms atheory about the extinction of the passenger pigeon D. Cast doubt on the conclusion reached by the archaeologists who conducted the studies discussed in the passage E. Counter an objection to an interpretation of the data obtained from Cahokian sites 8. Which of the following, if true, would most call into question the reasoning of "the archaeologists conducting the studies"? A. Audubon was unable to correctly identify twelfth-century Cahokian sites. B. Audubon made his observations before passenger pigeon populations began to decline. C. Passenger pigeons would have been attracted to household food trash. D. Archaeologists have found passenger pigeon remains among food waste at eighteenth-century human settlements. E. Passenger pigeons tended not to roost at the same sites for very many generations. In 1995 the Galileo spacecraft captured data about Jupiter’s atmosphere--namely, the absence of most of the predicted atmospheric water--that challenged prevailing theories about Jupiter’s structure. The unexpectedness of this finding fits a larger pattern in which theories about planetary composition and dynamics have failed to predict the realities discovered through space exploration. Insteadof "normal planets" whose composition could be predicted by theory, the planets populating our solar system are unique individuals whose chemical and tectonic identities were created through numerous contingent events. One implication of this is that although the universe undoubtedly holds other planetary systems, the duplication of the sequence that produced our solar system and the development of life on Earth is highly unlikely. Recently planetary scientists have suggested that the external preconditions for the development of Earth’s biosphere probably included four paramount contingencies. First, a climate conducive to life on Earth depends upon the extraordinarily narrow orbital parameters that define a continuously habitable zone where water can exist in a liquid state. If Earth’s orbit were only 5 percent smaller than it is, temperatures during the early stages of Earth’s history would have been high enough to vaporize the oceans. If the Earth-Sun distance were as little as 1 percent larger, runaway glaciation on Earth about 2 billion years ago would have caused the oceans to freeze and remain frozen to this day. Second, Jupiter’s enormous mass prevents most Sun一bound comets from penetrating the inner solar system. It has beenestimated that without this shield, Earth would have experienced bombardment by comet-sized impactors a thousand times more frequently than has actually been recordedduring geological time. Even if Earth’s surface were not actually sterilized by this bombardment, it is unlikelythat any but the most primitive life-forms could have survived. This suggests that only planetary systems containing both terrestrial planets like Earth and gas giants like Jupiter might be capable of sustaining complex life-forms. Third, the gravitational shield of thegiant outer planets, while highly efficient, must occasionally fail to protect Earth. Paradoxically, whilethe temperatures required for liquid water exist only inthe inner solar system, the key building blocks of life, including water itself, occur primarily beyond the asteroid belt. Thus the evolution of life has depended on afrequency of cometary impacts sufficient to convey water,as well as carbon and nitrogen, from these distant regions of the solar system to Earth while stopping short of an impact magnitude that would destroy the atmosphere and oceans. Finally, Earth’s unique and massive satellite, the Moon, plays a crucial role in stabilizing the obliquityof Earth’s rotational axis, This obliquity creates the terrestrial seasonality so important to the evolution and diversity of life. Mars, in contrast, has wildlyoscillating tilt and chaotic seasonality, while Venus, rotating slowly backward, has virtually no seasonality at all. 9. The passage is primarily concerned with A. Enumerating conditions that may have been necessary for a particular development B. Outlining the conditions under which scientists may be able to predict certain events C. Explaining how a particular finding affected scientists ’understanding of a phenomenon D. Suggesting reasons why a particular outcome was more likely to occur than other possible outcomes E. Assessing the relative significance of factors that contributed to a particular occurrence 10. It can be inferred from the passage that the "planetary scientists" would be mostlikely to agree with which of the following statements concerning the development of complex life forms on Earth?A. It might have occurred earlier in Earth’s history if cometary impacts had been less frequent than they were.B. It could have occurred if Earth’s orbit were 1 percent larger than it is but not if Earth’s orbit were 5 percentsmaller C. It probably follows a pattern common onother terrestrial planets that occupy planetary systems containing gas giants. D. Its dependence on the effect that Jupiter’s gravitational shield has on Earth was difficult to recognize prior to 1995. E. It has been contingent on conditions elsewhere in Earth’s solar system as well as on conditions on Earth itself. 11. Theauthor of the passage most likely mentions Mars’"oscillating tilt" primarily in order to A. Provide evidence for a proposition about the potential effects of cometary impacts B. Emphasize the absence from oursolar system of "normal planets" C. Contrast the rotational axis of Mars with that of Venus D. Characterize the role of other planets in the solar systemin earth’s development E. Emphasize the importance of the Moon to the development of life on Earth 12. The passage suggests each of the following about water on Earth except: A. It was conveyed to Earth by comets B. It appeared on Earth earlier than did carbon and nitrogenC. Its existence in a liquid state is contingent on Earth’s orbital parametersD. Much of it came from a part of the solar system where water cannot exist in a liquid stateE. It is unlikely that there would be much of it available to support life if the gravitational shield of the outer planets did not limit the frequency with which comets strike Earth。

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Journal of Ethnopharmacology 138 (2011) 530–536Contents lists available at SciVerse ScienceDirectJournal ofEthnopharmacologyj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /j e t h p h a rmBiomarkers in the early period of acute myocardial infarction in rat serum and protective effects of Shexiang Baoxin Pill using a metabolomic methodPeng Jiang a ,Weixing Dai a ,Shikai Yan b ,Zhongliang Chen c ,Ruilin Xu c ,Jianmi Ding c ,Li Xiang a ,Shuping Wang a ,Runhui Liu a ,∗,Weidong Zhang a ,b ,∗∗aSchool of Pharmacy,Second Military Medical University,Shanghai 200433,PR China bSchool of Pharmacy,Shanghai Jiao Tong University,Shanghai 200030,PR China cShanghai Hutchison Pharmaceuticals Company,Shanghai 200331,PR Chinaa r t i c l ei n f oArticle history:Received 24February 2011Received in revised form 12September 2011Accepted 18September 2011Available online 1 October 2011Keywords:Biomarkers SerumEarly periodMyocardial infarction MetabolomicTraditional Chinese medicinea b s t r a c tEthnopharmacological relevance:To identify the biomarkers in early period of acute myocardial infarction (AMI)in rat serum and reveal the effective mechanism of a Traditional Chinese Medicine (TCM)named Shexiang Baoxin Pill (SBP).Material and method:A metabolomic approach using reversed-phase liquid chromatography/quadrupole time-of-ﬂight mass spectrometry (LC-Q-TOF-MS)was developed.Results:Fourteen biomarkers in the early period of acute myocardial infarction (AMI)in rat serum were identiﬁed.These biomarkers include 5-methylcytosine,cystathionine ketimine,2-oxoadipic acid,thymidine,epinephrine,homocystine,uric acid,12(S)-hydroperoxyeicosatetraenoic acid (12s-HPETE),11-dehydrocorticosterone,12(S)-hydroxyeicosatetraenoic acid (12s-HETE),deoxycorticosterone,cor-ticosterone,aldosterone and cortisol.Through pathway analysis of these biomarkers,inﬂammation,hypertrophy and oxidative injury were considered the most relevant pathological changes in early period of AMI.Conclusion:Identiﬁcation of AMI biomarkers not only supplied a systematic view of the progression of AMI in the early period but also provided the theoretical basis for the prevention or treatment of AMI.The results demonstrated that SBP pretreatment could offer protective effects for AMI through regulating the pathway of steroid hormone biosynthesis.© 2011 Elsevier Ireland Ltd. All rights reserved.1.IntroductionCardiovascular diseases (CVDs)are the world’s largest killers and will claim 23.6million lives by 2030according toAbbreviations:SBP,Shexiang Baoxin Pill ;AMI,acute myocardial infarction;TCM,traditional Chinese medicine;CVs,cardiovascular diseases;LC–MS,liq-uid chromatography–mass spectrometry;NMR,nuclear magnetic resonance;LADCA,left anterior descending coronary artery;HPLC,high performance liq-uid chromatography;LDH,lactate dehydrogenase;CKs,creatine kinases;ECGs,electrocardiograms;CMC-Na,carboxymethyl cellulose sodium salt;QC,quality control;LC–Q-TOF-MS,liquid chromatography–quadrupole-time of ﬂight-mass spectrometry;ESI,electrospray ionization;ANOVAs,one-way analyses of vari-ance;RSD,relative standard deviation;PLS-DA,partial least squares-discriminate analysis;LVs,latent variables;VIP,variable importance plot;AA,arachidonic acid;12(S)-HPETE,12(S)-hydroperoxyeicosatetraenoic acid;12(S)-HETE,12(S)-hydroxyeicosatetraenoic acid.∗Corresponding author.Fax:+862181871245.∗∗Corresponding author at:School of Pharmacy,Second Military Medical Univer-sity,No.325Guohe Road,Shanghai 200433,PR China.Fax:+862181871244.E-mail addresses:lyliurh@ (R.Liu),wdzhang@ (W.Zhang).the report of World Health Organization (http://www.who.int/mediacentre/factsheets/fs317/en/index.html ).Most CVDs such as angina,arrhythmias and heart failure are associated with the for-mation of acute myocardial infarctions (AMIs).Though previous studies have identiﬁed some important biomarkers such as tro-ponin I and T for the early diagnosis of AMI (Apple and Wu,2001),the mortality induced by AMI is still high.Further investigation to achieve an understanding of the biological process of AMI is there-fore still needed to ﬁnd new biomarkers and illuminate the disease mechanism.Because the earlier detection and treatment of AMI can greatly decrease the mortality and morbidity of patients,the iden-tiﬁcation of the related biomarkers in the early period of AMI will be important.Metabolomics is a newly developed method which can be used to monitor the changes of metabolites in bioﬂuids.Through identiﬁcation technology such as liquid chromatography–mass spectrometry (LC–MS)and nuclear magnetic resonance (NMR),the metabolite proﬁles will be established.Then,by using multivariate analysis,screening the data from metabolite proﬁles will become possible and identiﬁcation of potential biomarkers related to the0378-8741/$–see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.jep.2011.09.049P.Jiang et al./Journal of Ethnopharmacology138 (2011) 530–536531changes in the physiological state will also become possible.The identiﬁed metabolites may be successfully incorporated into clin-ical practice in the future.Metabolomics has been applied to the prediction of many diseases such as septemia and hepatotoxicity (Xu et al.,2008;Wang et al.,2008).Though some biomarkers related to AMI have been identiﬁed using a metabolomics method in recent years(Zhang et al.,2009; Lv et al.,2010;Yao et al.,2010),the metabolites that changed in the early period of AMI had still not been investigated.To achieve a complete understanding of the metabolite proﬁle associated with AMI in the early period,an AMI model using the left anterior descending coronary artery(LADCA)ligation method was adopted, and then the serum biomarkers were analyzed after5h of the heart operation using a metabolomic method.Shexiang Baoxin Pill(SBP),which consists of seven medicinal materials including Moschus,Radix Ginseng,Calculus Bovis,Cortex cinnamomi,Styrax,Venenum Bufonis and Borneolum Syntheticum,is a widely used traditional Chinese medicine(TCM)in clinical prac-tice for the treatment of AMI(Song et al.,2002;Wu et al.,2005; Yang et al.,2005;Ye,2006).SBP was also ofﬁcially recorded in the 2010edition of the Chinese pharmacopoeia(Editorial Committee of Pharmacopoeia of Ministry of Health PR China,2010).To elucidate its intervention effects and the mechanism of AMI,the established metabolomic method was also adopted.2.Experiment2.1.MaterialsHigh performance liquid chromatography(HPLC)-grade ace-tonitrile and formic acid were purchased from JT Baker(NJ,USA). Ultrapure water from a Milli-Q50SP reagent water system(Milli-pore Corporation,MA,USA)was used for the preparation of samples and mobile phase.The assay kits for lactate dehydrogenase(LDH) and creatine kinase(CK)were purchased from Nanjing Jiancheng Bio-engineering Institute(Nanjing,China).Commercial standards were purchased from Sigma/Aldrich(MO,USA).SBP was kindly offered by Shanghai Hutchison Pharmaceuticals Company(Shang-hai,China).2.2.Animal and MI modelTwenty male Sprague-Dawley rats(200±15g)were purchased from the Slac Laboratory Animal Co.,Ltd.(Shanghai,China).The animals were housed in stainless steel metabolic cages with free access to food and tap water under standard conditions of humidity (50±10%),temperature(25±2◦C)and12h light–dark cycle.The animals were acclimatized to the facilities for5days.All animals were handled with humane care throughout the experiment.The AMI model was established by LADCA ligation,as described previously(Wang et al.,2002).The chest was opened by a mid-dle thoracotomy under sterile conditions.After pericardiotomy,the heart was rapidly exteriorized and a4-0black silk ligature was then placed under the LADCA to form an occlusion.Three rats died before collecting serum.Seventeen rats survived,including11AMI rats and6control rats(without ligation).All the rats wereﬁxed on pad in a position on the back and two-lead electrocardiograms (ECGs)were recorded by the MPA2000biosignal analytical system (Shanghai Alcott Biotech Co.,Ltd.,Shanghai,China)after5h of the heart operation.2.3.Drug administration and sample collectionAccording to the clinical dosage of SBP(2.25mg/kg/d),6of 11AMI rats were treated with SBP at a dosage of14mg/kg/d by oral gavage on4consecutive days before LADCA ligation(Wang Table1HPLC gradient elution programme.Time(min)A%(0.1%formic acid in H2O)B%(acetonitrile)097338020640601240601320801429820298et al.,2004;Hu et al.,2009).SBP was ground into aﬁne pow-der and dissolved in0.5%carboxymethyl cellulose sodium salt (CMC-Na)aqueous solution(2.8mg/mL).Isocyatic CMC-Na aque-ous solution was administered orally to control(n=6)and AMI (n=5)rats.Serum was immediately collected from the ophthalmic venous plexus after recording ECGs.The collected serum was divided into two parts.One part was used for the analysis of serum concentrations of LDH and CK,and the other part was used for the metabolomic analysis.Serum concentrations of LDH and CK were measured by UV1100ultraviolet spectrophotometer(Beijing Rayleigh Analytical Instrument Corp.,Beijing,China).The experiment was carried out in accordance with the guide-lines of the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources of Shanghai,China. The study protocol was approved by the Animal Care and Use Com-mittee of the Second Military Medical University.2.4.Sample preparationFor LC–MS analysis,50␮L of rat serum was extracted with 150␮L acetonitrile.After vortex-mixing for30s,these samples were centrifuged at12,000rpm for10min to remove proteins.The supernatant was then transferred to autosampler vials.To ensure the stability of sequence analysis,a quality control (QC)sample was prepared by pooling the same volume(10␮L) from each serum sample and then preparing the pooled QC sam-ple in the same way as the samples.The pooled QC sample was analyzed randomly through the analytical batch.In addition,six aliquots of serum sample from the same rat were treated in the same process to validate the repeatability of the sample preparation method.2.5.Conditions of liquid chromatography–quadrupole-time ofﬂight-mass spectrometry(LC–Q-TOF-MS)Metabolomic analysis was performed on an Agilent-1200LC system which was coupled with an electrospray ionization(ESI) source(Agilent Technologies,Palo Alto,CA,USA)equipped with an Agilent-6520accurate-mass Q-TOF mass spectrometer.The sepa-ration of all samples was performed on an Eclipse Plus C18column (1.8␮m,2.1mm×100mm,Agilent)with a column temperature maintained at40◦C.Theﬂow rate was0.3mL/min and the mobile phase consisted of ultrapure water with0.1%formic acid(A)and acetonitrile(B).The gradient programme is shown in Table1.The sample injection volume was3␮L.The mass spectrometer was operated in both positive and neg-ative ion modes with parameters set as follows:drying gas(N2)ﬂow rate,8L/min;gas temperature,330◦C;pressure of nebulizer gas,35psig;V cap,4000V;fragmentor,160V;skimmer,65V;scan range,m/z50–1000.The MS/MS analysis was acquired in the tar-geted MS/MS mode with collision energy ranging from5V to20V.532P.Jiang et al./Journal of Ethnopharmacology138 (2011) 530–536Table2Concentrations of major serum enzymes in the control,AMI and SBP treatment groups.Group LDH(U/L)CK(U/L)Control1778±4414242±1070 AMI2673±669**8828±2281** SBP treatment2058±588#5406±1196##**Signiﬁcant difference compared with control group(P<0.01).#Signiﬁcant difference compared with AMI groups(P<0.05).##Signiﬁcant difference compared with AMI groups(P<0.01).2.6.Method validationThe newly developed LC–Q-TOF-MS method needed to be val-idated.The stability and repeatability of this experiment were determined.According to the different chemical polarities and mass values,theﬁve extracted ions of mass184.0897(epinephrine, positive mode),125.0592(5-methylcytosine,positive mode), 167.0292(uric acid,negative mode),329.2202(deoxycorticos-terone,negative mode)and359.1938(aldosterone,negative mode) were selected for validation.Extracts from six aliquots of a random serum sample were con-tinuously injected to evaluate the repeatability.The data acquired from six QC samples(three unknown samples injected with one QC sample)were used to validate the LC–MS system stability for the large-scale sample analysis.The peak area and retention time (RT)ofﬁve extracted ions were then analyzed to determine the variation.2.7.Data processingThe raw LC–MS data for all samples(exclude the data from blank samples)wereﬁrstly processed by the Agilent Mass Hunter Qualitative Analysis Software(Agilent Technologies,Palo Alto,CA, USA).Theﬁlter parameters were set as follows:restrict retention time,0.2–14min;restrict mass,80–1000amu;peak relative height,≥1.5%;mass tolerance,0.05Da;retention time windows,0.1min. After beingﬁltered,a peak table was created which included the information of the retention time,mass and ion intensity for all identiﬁed components.The data from each sample were then nor-malized to total area and all data were imported into the software SIMCA-P(Ver.11,Umetrics,Umea,Sweden)where multivariate analyses such as partial least squares-discriminate analysis(PLS-DA)were used for calculation.The signiﬁcance was expressed by using one-way analyses of variance(ANOVAs)with a Bonferroni correction in the SPSS13.0for Windows(SPSS Inc.,Chicago,IL,USA). P values less than0.05were considered signiﬁcant.3.Results and discussion3.1.ECG and sero-enzyme testIn this study,typical ECG alterations such as oblique and upward ST segment elevation and broad T wave were detected in all AMI rats after5h of heart surgery.The changes in ECGs deﬁnitely demonstrated that the model was successful.Furthermore,the serum concentration of LDH and CK,which have been cited as important parameters in the assessment of myocardial injury(Zheng et al.,2004),were also analyzed to evalu-ate the validity of the AMI model and the effect of SBP pretreatment. As shown in Table2,compared with control rats,the concentrations of LDH(P<0.01)and CK(P<0.01)in AMI model rats were signiﬁ-cantly increased,an effect that can be reversed by the intervention of SBP administration.The enzymatic results demonstrated that the AMI model was reliable and the intervention of SBP was positively effective.3.2.Optimization of LC–MSMetabolomics aims to pinpoint the interesting metabolites in a complex metabolite proﬁle,so the process of sample pretreat-ment should be minimized to avoid the loss of potential biomarkers. To optimize the pretreatment method,deproteinating by adding acetonitrile was compared to deproteinating by adding methanol. Results showed that deproteinating by adding acetonitrile gave more ion information than adding methanol.So serum samples were deproteinated by adding acetonitrile before LC–Q-TOF-MS analysis.Theﬂow rate was set at0.3mL/min because the chromatograms showed better resolution of adjacent peaks.The column tempera-ture was set to40◦C to reduce the higher column pressure.Studies also showed that0.1%formic acid added into the mobile phase (water)can obtain better separation of chromatographic peaks.To obtain the full knowledge of the metabolite proﬁle in rat serum,both positive and negative chromatograms were recorded in this study.The drying gasﬂow rate and gas temperature were set at8L/min and330◦C,respectively,to obtain the best ioniza-tion efﬁciency.The collision energy was optimized from5to20eV according to the chemical structure of potential biomarkers for MS/MS spectral analysis in both positive and negative mode.3.3.LC–Q-TOF-MS method validationThe data for system repeatability and stability of the proposed method are listed in Table3.In the validation of system repeatabil-ity,a stable retention time(RT)forﬁve selected ions in six batches of serum samples was observed with the variations less than0.83% relative standard deviation(RSD)in positive mode and0.77%RSD in negative mode.In addition,the RSD values for peak areas for the main ions were varied from9.11to10.04%in positive mode and from7.03to10.88%in negative mode.The validation data acquired from the QC sample also showed good system stability.The RSD(%)of peak areas and RT of the main ions were0.48–0.99%for RT and9.91–10.79%for peak areas in the positive mode(0.53–0.91%for RT and5.61–12.74%for peak areas in the negative mode).Table3The repeatability and stability data for the proposed method.Mode Selected ions(mass)Repeatability(n=6)Stability(n=6)RT(min)Peak area RT(min)Peak areaMean RSD(%)Mean RSD(%)Mean RSD(%)Mean RSD(%)ESI(+)125.0 1.350.8325339.11 1.330.9933519.91 183.1 5.940.67556210.04 5.920.48318710.79ESI(−)168.0 1.670.6976497.03 1.660.534569 5.61 330.315.820.7251248.2915.720.6736537.17 360.316.990.77183510.8816.940.91130712.74P.Jiang et al./Journal of Ethnopharmacology138 (2011) 530–536533 Table4Fourteen identiﬁed biomarkers of AMI detected by LC–Q-TOF-MS in both positive and negative ionization modes.Mode Number RT(min)Exact mass Formula Compound Trend aESI(+)1 1.34125.0584C5H7N3O5-Methylcytosine↓2 1.85203.0247C7H9NO4S Cystathionine ketimine↑3 5.76160.0370C6H8O52-Oxoadipic acid↓4 5.81242.0913C10H14N2O5Thymidine↓5 5.96183.0891C9H13NO3Epinephrine↑ESI(−)6 1.58268.0557C8H16N2O4S2Homocystine↑7 1.69168.0288C5H4N4O3Uric acid↑813.32336.2303C20H32O412S-HPETE↑915.58344.1984C21H28O411-Dehydrocorticosterone↑1015.83320.2355C20H32O312S-HETE↑1116.34330.2197C21H30O3Deoxycorticosterone↑1216.97346.2147C21H30O4Corticosterone↑1316.97360.1932C21H28O5Aldosterone↑1417.69362.2091C21H30O5Cortisol↑a“↑”and“↓”represent the compound as up-and downregulated in the AMI group compared with the control group.All results indicated that the established LC–MS method could be used for analyzing the large-scale samples in the metabolomic studies.3.4.Identiﬁcation of biomarkers in the early period of AMI in ratsBecause a large number of signals were obtained from the serum samples,a multivariate analysis method was needed to dis-criminate the ions which contribute to the classiﬁcation of the control and AMI groups.Therefore,PLS-DA,a supervised projection method,was applied to the LC–MS data in this study.The estab-lished PLS-DA model using cross-validation could describe72.8% of the variation in X(R2X=0.728)and89.9%of the variation in the response Y(class)(R2Y=0.899)with a predictive ability of85.1% (Q2Y=0.851).Latent variables(LVs)of the PLS-DA model were also determined during cross-validation in Smica P11.0.In this model, 2LVs were calculated during cross-validation in SIMCA P11.0.The cross-validation results showed that a well-ﬁtting PLS-DA model had been established.As shown in Fig.1A,the score plot showed that AMI and the control groups could be classiﬁed clearly.The corresponding load-ing plot showed the contribution of the variables to the differences between AMI samples and the control groups(Fig.1B).The more the variable deviates from the origin,the higher the value of the variable importance plot(VIP)that will be obtained.Therefore, the potential biomarkers in the early period of AMI are found in those variables that obviously deviate from the origin.Inthis Fig.1.PLS-DA model of the AMI.(A)Score plot of control(red dots)and model(black squares)groups obtained from rat serum samples.(B)Loading plot obtained using Pareto scaling with mean centering.Each triangle represents an ion.(For interpre-tation of the references to color in thisﬁgure legend,the reader is referred to the web version of the article.)Table5The summary of intensity values for potential biomarkers in the control group and in the model group.Biomarkers Peak intensity(mean±SD)Control(n=6)Model group(n=5)SBP treated group(n=6)5-Methylcytosine100.71±11.8363.24±6.45**81.23±5.07**,## Cystathionine ketimine51.34±3.97124.58±12.59**100.46±13.21**,##2-Oxoadipic acid57.26±6.3333.14±10.00**42.96±7.99**,## Thymidine89.34±5.7857.48±12.34**72.14±4.62**,## Epinephrine305.27±44.01397.45±43.25**307.54±22.88## Homocystine266.75±30.85360.81±37.17**299.17±17.23##Uric acid176.99±23.30256.62±20.76**213.90±21.16**,##12S-HPETE344.71±52.03428.81±11.09**397.26±21.40*,#11-Dehydrocorticosterone350.19±17.77472.02±47.55**409.73±22.50**,##12S-HETE359.82±21.07435.40±17.82**390.05±19.12**,## Deoxycorticosterone206.04±9.90362.15±16.30**300.43±7.59**,## Corticosterone170.30±36.82235.62±21.80**172.09±17.47## Aldosterone72.77±10.11140.37±36.97**71.65±6.24## Cortisol224.46±33.25317.86±14.14**230.73±19.04##*Signiﬁcant difference compared with control group(P<0.05).**Signiﬁcant difference compared with control group(P<0.01).#Signiﬁcant difference compared with AMI group(P<0.05).##Signiﬁcant difference compared with AMI group(P<0.01)534P.Jiang et al./Journal of Ethnopharmacology 138 (2011) 530–536Fig.2.MS/MS spectrum of thymidine (the precursor ion was mass 243.09;the major fragment was mass 127.08):(A)serum sample,(B)standard.study,a total of 42variables (the value of VIP >1.0)contributed to the metabolic variation.Among these variables,14(5in posi-tive mode,9in negative mode)were predicted by comparing the MS and MS/MS fragments with the metabolites found by search-ing in databases ( ,http://www.hmdb.ca/)and subsequently conﬁrmed by the use of commercial standards (Table 4).The summary of intensity values for potential biomark-ers in the control group,the model group and the SBP-treated group are shown in Table 5,and one-way ANOVAs with a Bonferroni cor-rection were used to validate the signiﬁcance.An identiﬁed biomarker produced the quasi-molecular mass at mass 243.0920(the retention time was 5.76min in the positive mode).C 10H 14N 2O 5was subsequently calculated as the most probable molecular formula.The tandem MS fragment at mass 127.0899yielded the molecular structure information (Fig.2).The above information was also searched in the Internet databases mentioned above.Considering the molecular’s elemental composi-tion,fragment information and retention time behaviour together,the ion of mass 243.0920was tentatively identiﬁed as thymidine.The identiﬁcation was conﬁrmed by comparison with the commer-cial ing this iterative method,another 13biomarkers were identiﬁed (Table 4).3.5.Biomarkers and their pathwaysAmong those 14identiﬁed biomarkers,3were depressed in AMI rat serum,and another 11were elevated.The related pathway of every biomarker was also recorded in Table 5by searching KEGG PATHWAY Database (http://www.genome.jp/kegg/).SeverallinesFig.3.Hypertrophy-related biomarkers in the steroid hormone biosynthesis path-way (the skeleton diagram represents identiﬁed biomarkers).of evidence have demonstrated that 11of 14identiﬁed biomarkers in this study play an important role in the formation of AMI.These 11biomarkers mainly participate in three pathological processes,including inﬂammation,hypertrophy and oxidative injury,which are all activated as an insult by AMI (Table 6).The increasing level of homocysteine in serum has been shown to be associated with an increased risk for occlu-sive vascular disease (Olszewski and Szostak,1988;Chambers and Kooner,2001).Welch and Losculzo (1998)reported that homocysteine probably leads to oxidative damage of endothelial cells because of the reactive oxygen radicals that are produced during auto-oxidation of homocysteine in plasma.Poddar (2001)demonstrated that homocysteine also promotes the recruitment of leucocytes,thereby enhancing the injury to the endothelial cells.Myocardial infarction is associated with tissue-speciﬁc acti-vation of the myocardial aldosterone synthesis (Silvestre et al.,1999).The increasing level of aldosterone may lead to the forma-tion of hypertrophy,ventricular remodeling and even heart failure.At present,aldosterone antagonists have been used widely for patients with post-myocardial infarction heart failure in clinic.In addition,as the results of other studies showed (citations shown in Table 5),the higher serum levels of 11-dehydrocorticosterone,deoxycorticosterone,corticosterone and cortisol,which all par-ticipate in the formation of hypertrophy,were also observed in this experiment.As aldosterone,11-dehydrocorticosterone,deoxy-corticosterone,corticosterone and cortisol are in the pathway of steroid hormone biosynthesis,steroid hormone biosynthesis appears to be acutely perturbed in the early period of AMI.The hypertrophy-related biomarkers in the pathway of steroid hor-mone biosynthesis are shown in Fig.3.Fig.4.Resulting scores plot from PLS-DA of LC–Q-TOF-MS data obtained from con-trol rats’(blue diamonds),AMI rats’(red dots)and SBP pretreatment rats’(black squares)serum samples.(For interpretation of the references to color in this ﬁgure legend,the reader is referred to the web version of the article.)P.Jiang et al./Journal of Ethnopharmacology 138 (2011) 530–536535Table 6Related pathway and pathological processes for fourteen identiﬁed biomarkers.CompoundRelated pathwayContribution to AMI5-MethylcytosinePyrimidine metabolism–Cystathionine ketimine Cysteine and methionine metabolism Oxidative injury (Zhang et al.,1999)2-Oxoadipic acid Lysine degradation–Thymidine Pyrimidine metabolism –Epinephrine Tyrosine metabolismHypertrophy (Rapacciuolo et al.,2001)Homocysteine Cysteine and methionine metabolism Oxidative injury (Welch and Losculzo,1998)Uric acid Purine metabolism Oxidative injury (Glantzounis et al.,2005;Strazzullo and Puig,2007)12S-HPETEAA metabolismInﬂammation (Funk,2006;Wen et al.,2007)11-Dehydrocorticosterone Steroid hormone biosynthesis Hypertrophy (Sheppard and Autelitano,2002;Lister et al.,2006)12S-HETEAA metabolismInﬂammation (Funk,2006;Wen et al.,2007)Deoxycorticosterone Steroid hormone biosynthesis Hypertrophy (Yang and Nickerson,1988)Corticosterone Steroid hormone biosynthesis Hypertrophy (Scheuer and Mifﬂin,1997;Antonov et al.,2000)Aldosterone Steroid hormone biosynthesis Hypertrophy (Silvestre et al.,1999;Remme,2001)CortisolSteroid hormone biosynthesisHypertrophy (Lumbers et al.,2005;Porrello et al.,2008)Fig.5.Mean levels of 4biomarkers completely reversed by SBP in control,AMI and SBP pretreatment groups.One-way ANOVA with a Bonferroni correction was used.**Signiﬁcant difference compared with control group (P <0.01);##signiﬁcant difference compared with AMI groups (P <0.01).Several studies have demonstrated that ischaemia results in the accumulation of unesteriﬁed arachidonic acid (AA)via the action of membrane-bound phospholipases (Gross et al.,2005;Hjelte and Nilsson,2005).The compounds 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE)and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE)are both metabolites of AA.The high levels of 12(S)-HPETE and 12(S)-HETE reﬂected the activation of AA metabolism and contributed to the inﬂammatory reaction in AMI.In summary,the 14identiﬁed biomarkers in the early period of AMI rats not only revealed a new insight into the AMI network in vivo but also supplied the theoretical basis for the prevention or treatment of AMI.The multiple pathways included in this study also demonstrated the complicated mechanism of AMI.3.6.Metabolomic study of SBP pretreatmentThe protective effects of SBP for the treatment of AMI can be obtained not only from Section 3.1but also can be demon-strated using metabolomic methods.The newly established PLS-DA model of two PLS-components was signiﬁcant according to cross-validation (R 2X =0.646,R 2Y =0.924and Q 2Y =0.879).The score plot of the PLS-DA model (Fig.4)showed that control,AMI and SBP pretreatment groups are classiﬁed clearly,and the SBP pretreatment group is closer to the control group than the AMIgroup,which might suggest that SBP can reverse the pathological process of AMI.By comparing the identiﬁed biomarker level in AMI,control and SBP pretreatment groups,four of the identiﬁed biomarkers,including corticosterone,aldosterone,cortisol and epinephrine,are completely reversed by SBP (shown in Fig.5).All of the reversed biomarkers are the metabolites of steroid hormone biosynthesis and contribute to the formation of hypertrophy.These results showed that SBP pretreatment could depress the path-way of steroid hormone biosynthesis and decrease the level of hypertrophy-related metabolites,thereby inhibiting the patholog-ical changes of hypertrophy and protecting the impaired heart.The results of histopathology and metabolomics clearly demon-strate that SBP has protective effects on AMI.The effects of SBP pretreatment partially depend on inhibiting the biosynthesis of steroid hormones.4.ConclusionIn this study,14metabolites were identiﬁed as potential biomarkers in the early period of AMI in rat serum,and the steroid hormone biosynthesis (11-dehydrocorticosterone,deoxycorticos-terone,corticosterone,aldosterone and cortisol)was the acutely perturbed pathway in the early period of AMI.The identiﬁed biomarkers not only revealed a new insight into the AMI network in vivo but also supplied the theoretical basis for the prevention。