Fundamental hair follicle biology and fine fibre production

小学上册英语第4单元自测题[含答案]考试时间：80分钟（总分:120）B卷一、综合题(共计100题共100分)1. 听力题：A _______ is a large body of saltwater.2. 选择题：What is the name of the closest galaxy to our Milky Way?A. AndromedaB. TriangulumC. WhirlpoolD. Sombrero3. 听力题：The ______ is a famous explorer.4. 听力题：The ______ is known for its intelligence and problem-solving skills.5. 选择题：What do you call a story that is made up?A. FictionB. Non-fictionC. BiographyD. Autobiography答案:A6. 填空题：The __________ (探险故事) inspire many people.7. 听力题：The process by which plants convert sunlight into energy is called _______.8. 填空题：The _____ (绿叶) provide energy for the plant.Which animal is known for its ability to change colors?A. ChameleonB. FrogC. DogD. Cat10. 填空题：Every summer, I go to _______ (地方) for vacation. It’s a wonderful way to _______ (放松).11. 填空题：The children are _______ (在玩游戏).12. 填空题：The __________ (历史的回响) echoes through generations.13. 选择题：What do we call the study of the human mind?A. PsychologyB. SociologyC. PhilosophyD. Anthropology答案: A. Psychology14. 听力题：A ______ is a type of insect that can be very loud.15. 填空题：Planting trees can provide ______ (遮荫) and cooling effects.16. 填空题：A healthy plant will have vibrant ______ and sturdy stems. (健康的植物会有鲜艳的叶子和坚固的茎。

新托福阅读材料：了解我们的头发小马过河为大家准备了“新托福阅读材料：了解我们的头发”，供各位备考托福的考生们参考使用，来提高自己的托福成绩！免费咨询电话：400-0123-267头发，枯了不痒，剪了不疼，那头发是做什么用的?是为了美观?还是为了御寒?这些回答都不全面，下面，就请跟着新东方留学，进入今天的托福阅读材料，来详细了解一下我们的头发。

A human hair consists mainly of a protein called Keratin. It also contains some moisture and the trace metals and minerals found in the rest of the body.人类的头发主要由一种叫角朊的蛋白质组成，并含有水分及在身体其他部分也可找到的微量金属和矿物质。

● The only living part of hair is underneath the scalp--when the hair had grown through the scalp it is dead tissue.头发唯一有生命的部分是在头皮下面，当它长出头皮时便成为无生命组织。

● Hair’s natural shine is supplied by its own conditioner, sebum, an oil composed of waxes and fats and also containing a natural antiseptic that helps fight infection. Too much sebum results in greasy hair and conversely, too little sebum makes dry hair.头发的自然光泽来自它自身的护发素：油脂，它含有蜡和脂肪，还含有抗感染的自然抗菌剂。

法国离子氧秀发的去屑革命头屑终结者随着市场不断发展，竞争激烈程度的加剧以及消费者需求的进一步提高和功能要求的细化，开发具有新性能和新功能的洗发水已经是大势所趋。

现代洗发水在注意安全性和稳定性的必要基础上，已向天然性、营养性、温和性、功能性和方便性方面发展。

然而这个广告漫天轰炸的时代，人们对商品的选择总有一种从众心理，无法抗拒琳琅满目的明星代言的洗发水，然而面对数之不尽的品牌不知如何选择时，洗发界迎来了一次全新的革命，这次革命从根本上解决了去屑、止痒、控油、防脱等基本问题。

正是这次革命，让洗发水进入了氧离子时代。

以天然、绿色、健康为一体，氧离子洗发水以迅雷不及掩耳之势风靡全球。

氧离子，诞生于2010年的法国，众所周知，阿尔卑斯山等众多山脉雪峰上生长着大量天然草本植物，而这些植物，已是护肤、护发产品中的重要材料。

56岁的法国生物学博士Maxence，几十年专注于研究天然草本植物。

他发现，这些草本植物之所以如此珍贵，得益于雪峰空气中的氧离子成分。

2010年，Maxence 得出一项重要成果：活性离子氧能迅速穿透细菌的细胞膜，与细胞酶发生不可逆反应，杀死细菌。

并且对人体皮肤无刺激，无副作用。

为了迎合中高端消费者群体对健康自然的追求，2011年，法国诞生了以氧离子和草本植物为主要成分的洗发水品牌，并迅速进入中国市场，也就是法国leeziyoung。

作为国内唯一的氧离子洗发水品牌，目前，leeziyoung洗发水主要是以产品的质量和成分的独特作为主要卖点。

产品中的活性离子氧、甲基异噻唑啉酮均是高效的杀菌剂，对于抑制微生物的生长有很好的作用，可以抑制细菌、去除头屑；而过氧化物歧化酶，能促进 B 型单胺氧化酶活性和红细胞的生成，有利于白发脱发的的治疗。

此外配方特别加入的法国雪峰珍贵草本，对头发的修复滋养，以及对头皮的保护都起到了极大的作用。

集去屑、止痒、控油、防脱多功效为一体的leeziyoung洗发水，面对各大占有中国大部分市场的明星品牌，以其消费者实用有效的口碑，在明星轰炸式的产品时代走出了属于自己的路线。

自然和植物给了我们美丽的秘密高丹丹【期刊名称】《《WTO经济导刊》》【年(卷),期】2016(000)002【总页数】2页(P28-29)【作者】高丹丹【作者单位】【正文语种】中文访谈嘉宾：娇韵诗集团亚太区公共事务总监 Berenice Voets“二战期间，一名外科医生在做手术的过程中发现：很多女性即使在痊愈后仍会因为伤疤而遗憾。

女性需要的不仅仅是治疗身体的创伤，还需要心灵的治愈。

于是，他开发了世界上第一瓶纯植物油，目的在于让女性在皮肤美丽的同时能感受到愉悦。

这位医生名叫贾克・古登，1954年，他凭着自己‘让世界更美丽’的梦想创立了娇韵诗（Clarins）”。

娇韵诗集团亚太区公共事务总监Berenice Voets带着些许自豪，向本刊记者讲述起创始人以及关于“美丽”的故事。

贾克・古登提出10个“美丽承诺”，提倡美丽的同时还应该对地球和子孙后代有责任感。

这也成为了娇韵诗的基本原则，每位娇韵诗人在工作的时候都要思考如何平衡工作和对自然的保护。

娇韵诗的成功的确和植物息息相关，在娇韵诗的产品中使用了多达250多种植物,其产品都是从自然中获得灵感，从植物中研发而来。

30多年前，娇韵诗在亚马逊流域、巴西开启了第一个生物多样性保护项目，之后在法国、巴西、秘鲁、泰国和中国等国家开展了更多类似的项目。

Berenice Voets说：“保护自然、保护珍稀植物是我们回馈自然的方式，因为自然和植物给了我们美丽的秘密，也给了我们产品创新的灵感。

”作为“美丽承诺”的一部分，娇韵诗从2010年开始运行“美丽种籽”计划的前身。

2014年11月，娇韵诗集团联合云南当地政府和滋根基金会（中国滋根乡村教育与发展促进会正式发起“美丽种籽”的生物多样性计划，并得到知名植物研究机构的专业支持。

Berenice Voets正是这一计划的发起人。

“美丽种籽”项目就设在云南老君山国家地质公园。

在云南的考察过程中，娇韵诗团队发现那里的人们和自然的关系非常和谐，这和娇韵诗尊重自然的理念是一致的。

As a high school student, Ive always been fascinated by the intricacies of the human body, and one aspect that particularly caught my attention is the care of hair follicles. Hair is not just a part of our appearance its a symbol of our health and vitality. Heres my take on how to maintain the health of our hair follicles, based on my own experiences and research.Firstly, understanding the basics of hair follicles is crucial. Hair follicles are tiny organs embedded in the skin that produce hair. They are sensitive to various factors, including diet, stress, and environmental conditions. When I started to notice my hair becoming dry and lifeless, I realized the importance of taking care of these tiny yet vital structures.One of the most effective ways Ive found to maintain healthy hair follicles is through a balanced diet. Nutrients like biotin, vitamin D, and proteins are essential for hair health. I made sure to include foods rich in these nutrients in my daily meals. For instance, eggs, nuts, and fish are great sources of protein and omega3 fatty acids, which are known to promote hair growth and strength.Another important aspect is hydration. Drinking plenty of water helps to keep the scalp moist, which is beneficial for hair follicles. I made it a habit to carry a water bottle with me everywhere I go, ensuring that I stay hydrated throughout the day.Stress management is another key factor in maintaining healthy hair follicles. High stress levels can lead to hair loss and poor hair growth. To combat this, I incorporated stressrelieving activities into my routine, suchas yoga and meditation. These practices not only helped me to relax but also improved the overall health of my hair.Using the right hair care products is also vital. I learned to choose products that are gentle on the scalp and hair. Harsh chemicals can damage hair follicles and lead to hair loss. I switched to natural, sulfatefree shampoos and conditioners, which were gentle on my hair and scalp.Regular scalp massages have been a gamechanger for me. Massaging the scalp helps to stimulate blood flow to the hair follicles, promoting hair growth. I make it a point to massage my scalp with a few drops of essential oils, like lavender or rosemary, for a few minutes every day. This not only feels relaxing but also helps to keep my hair follicles healthy.Protecting my hair from environmental damage is another step Ive taken. Sun exposure, pollution, and harsh weather conditions can all harm hair follicles. I started wearing a hat when going out in the sun and using a leavein conditioner to protect my hair from the elements.Lastly, Ive learned the importance of giving my hair a break from heat styling tools. Excessive use of hair dryers, curling irons, and straighteners can weaken hair and damage follicles. I try to limit my use of these tools and let my hair airdry whenever possible.In conclusion, taking care of hair follicles is a holistic process that involves a balanced diet, proper hydration, stress management, using gentle hair care products, regular scalp massages, protecting hair from environmentaldamage, and giving it a break from heat styling. By incorporating these practices into my daily routine, Ive noticed a significant improvement in the health and appearance of my hair. Its a small investment of time and effort that pays off in maintaining the beauty and health of our hair for a long time.。

Biology of the Hair Follicle:The BasicsKaroline Krause,MD,and Kerstin Foitzik,MDThe mammalian hair follicle represents a unique,highly regenerative neuroectodermal–mesodermal interaction system that contains numerous stem cells.It is the only organ in the mammalian organism that undergoes life-long cycles of rapid growth (anagen),regres-sion (catagen),and resting periods (telogen).These transformations are controlled by changes in the local signaling milieu,based on changes in expression/activity of a con-stantly growing number of cytokines,hormones,neurotransmitters,and their cognate receptors as well as of transcription factors and enzymes that have become recognized as key mediators of hair follicle cycling.Transplantation experiments have shown that the driving force of cycling,the “hair cycle clock,”is located in the hair follicle itself.However,the exact underlying molecular mechanisms that drive this oscillator system remain un-clear.These controls of hair follicle cycling are of great clinical interest because hair loss or unwanted hair growth largely reflect undesired changes in hair follicle cycling.To develop therapeutic agents for the management of these hair cycle abnormalities,it is critical to decipher and pharmacologically target the key molecular controls that underlie the enigmatic “hair cycle clock.”Semin Cutan Med Surg 25:2-10©2006Elsevier Inc.All rights reserved.KEYWORDS hair,follicle,clock,cycle,cytokines,hormones,neurotransmitters,modulatorsThe hair follicle is one of the most complex miniorgans of the human body.This exquisitely productive protein fi-ber factory,which doubles as a sensory organ and serves as an instrument of psychosocial communication,excretion,and protection,undergoes cyclic transformations between phases of rapid growth (anagen),apoptosis-driven regression (cata-gen),and relative quiescence (telogen).1With this “hair cy-cle,”the follicle demonstrates the unique ability to cyclically regenerate itself during our lifetime,based on epithelial–mes-enchymal interactions that drive waves of daughter cell pop-ulations,derived from resident epithelial,neural,and mes-enchymal stem cells,into defined strata of differentiation.2,3Hair loss,as well as unwanted hair growth (hirsutism,hypertrichosis),is a widespread problem.According to one calculation,androgenetic alopecia on its own eventually af-fects approximately 50%of the world’s adult population.4,5The hair shaft,the main product of the hair follicle,serves as an instrument of social communication,a protective device,and as a container for sequestering and excreting unwanted compounds.2,4Given the role of hair in psychosocial communication,(as a symbol of youth,health,fertility,and sexual potency)hair loss often has an underestimated psychosocial impact on an individual’s self-esteem,interpersonal relationships,and po-sitioning within a society.6Telogen effluvium,androgenetic alopecia,and alopecia areata,the 3most frequent hair loss disorders encountered in clinical practice,exemplify how a range of negative psychological and social experiences trans-late into significant stressors that possibly conspire to further aggravate hair loss.6-9And yet,there are still many general practitioners,and even dermatologists,who mistakenly view hair loss as a largely cosmetic problem.Most hair growth disturbances seen in clinical practice primarily result from changes in hair follicle cycling.Andro-genetic alopecia (AGA)in men and women is caused by a shortening of the anagen phase,with the clinical conse-quence of increased hair loss (telogen effluvium),accompa-nied by a transformation of terminal to vellus hair follicles.Vice versa,a prolonged anagen period can be seen in the conversion of vellus hair follicles into terminal hair follicles during hypertrichosis and hirsutism.2,4,10Thus,a more pro-found understanding of the molecular controls of hair follicle cycling and its underlying disturbances promises to lead to the development of more effective “hair drugs,”one of the prime challenges of modern hair research.Apart from the clinical importance of basic hair research,Department of Dermatology,University Hospital Hamburg-Eppendorf,Uni-versity of Hamburg,Hamburg,Germany.Address reprint requests to Kerstin Foitzik,MD,Department of Dermatol-ogy,University Hospital Hamburg-Eppendorf,University of Hamburg,Martinistra ␤e 52,D-20246Hamburg,Germany.E-mail:kfoitzik@21085-5629/06/$-see front matter ©2006Elsevier Inc.All rights reserved.doi:10.1016/j.sder.2006.01.002the hair follicle also offers an excellent,well-defined,easily manipulated and widely available biological test system for studying many key problems of general biology exemplarily (morphogenesis,proliferation,apoptosis,epithelial differen-tiation,pigmentation,angiogenesis,wound healing,stem cell biology,extracellular matrix remodeling,immune privilege, antiinfection defense,hormone synthesis,and metabolism).2 To emphasize just2examples,the hair follicle’s unusual immune system,which has been almost completely ignored by mainstream immunological research,offers a unique op-portunity for studying the generation,maintenance,loss,and restoration of areas of relative immune privilege.11,12Its amazing capacity for the generation of neurohormones and its sensitivity to key mediators of systemic stress responses designate it an ideal testing ground for probing the“brain–skin connection.”13Basic DataThe human scalp,eyebrows,and lashes consist of long,thick, medullated and pigmented terminal hair shafts,whereas the body is covered with short,thin and often unpigmented vel-lus hairs.Each of us displays an estimated total number of5 million hair follicles,of which80,000to150,000are located on the scalp.The hair length is defined by the duration of anagen,which lasts for2to6years.Approximately85%to 90%of all scalp hairs are within anagen follicles.Catagen lasts only for a few weeks,followed by the telogen phase, which lasts2to4months.The usual growth of scalp hair follicles(ie,the rate of hair shaft elongation)lies between0.3 and0.5mm per day and is dependent on proliferation and subsequent follicular-type differentiation of the matrix kera-tinocytes in the hair bulb.The thickness of the hair shaft is related to the size of the hair bulb,10which in turn is dictated by the volume of the hair follicle’s mesenchymal compo-nent.14Functional Hair Follicle Anatomy The mature anagen hair follicle is composed of a multicylin-dric stem that contains the hair shaft in its center and origi-nates as an oval hair bulb proximally(Fig.1).15Embraced by the hair bulb lies an onion-like structure,called the dermal papilla(DP)(sometimes referred to as the“follicular papilla”to avoid confusion with the most superficial region of the dermis).The DP functions as the“command center”of the hair follicle and determines thickness,length,and likely the hair cycle itself.3Each hair follicle consists of epithelial and mesenchymal parts.The epithelium is divided into an upper permanent region,distal to the arrector pili muscle(APM)and an inferior region(including the hair bulb),which dramatically reforms itself over the cycle(Fig.1).Apart from serving as hair shaft factory,the anagen hair bulb also provides the hair shaft’s trichocytes with melanin granules.Within the hair bulb is a population of cells with the highest proliferation rate in the human body:the keratinocytes of the hair matrix.These can differentiate into trichocytes,or cells of the inner root sheath (IRS).The outer root sheath(ORS),hair matrix,and hair shaft derive from epithelial stem cells in the bulge area,func-tioning as a pluripotent epithelial stem cell population for the skin(Fig.1).16-18The bulge stem cells not only form the secondary hair germ,which is involved in the generation of the new hair,but they can even be reconstituted by dediffer-entiating keratinocytes in response to wounding of the bulge area.11The size of the anagen hair bulb,the duration of anagen, and the hair shaft diameter are determined by the volume,the number of cells,and the secretory activity of the DP.19,20 Stringent coordination between epithelial and mesenchymal portions is needed to maintain the cyclic hair follicle growth.2 Mesenchymal stem cells within the tissue sheath serve as a recruitment pool for new DP cells.Apart from mesenchymal stem cells,the hair follicle also contains mast cell precur-sors21-23and neuronal stem cells,the latter of which can develop into neurons and blood vessels.24The large numbers of stem cells make the hair follicle a fascinating organ in the field of stem cell biology.The Hair CycleHair cycling is the rhythmic change of the hair follicle through phases of growth(anagen),regression(catagen),and rest(telogen).Synchronized hair follicle cycling(in mammals) prepares the hair coat for seasonal changes in habitat condi-tions as well as procreational activities.2The purpose of hair cycling in mammals with individual(asynchronous)follicle waves(eg,humans)is not as obvious,but may include clean-ing the skin surface of debris and parasites,and excretion of deleterious chemicals by encapsulation within trichocytes.2 In addition,follicle cycling might serve as a regulator of para-crine or even endocrine secretion of hormones and growth modulators produced within the follicle and secreted into the skin or circulation.3Finally,hair follicle cycling may act asa Figure1A,Anagen VI hair follicle.Histologic longitudinal section on the left hand side.Schematic drawing of an anagen VI follicle with anatomical details on the right hand side.B,Anagen VI hair bulb in detail(enlargement of schematic drawing in A).APM,arrec-tor pili muscle;CTS,connective tissue sheath;DP,dermal papilla; IRS,inner root sheath;ORS,outer root sheath;SG,sebaceous gland (modified after Whiting,2004).15Biology of the hair follicle3safe-guarding system against malignant degeneration by pro-tecting rapidly dividing keratinocytes from oxidative damage by deletion during catagen.3Anagen (the growth phase of the hair cycle)is divided into 6different stages defined by specific morphologic criteria (Fig.2).25The recurrent formation of the hair follicle displays morphologic and molecular analogies to fetal hair follicle morphogenesis.26Many molecular key regulators of hair bi-ology (members of the transforming growth factor (TGF)-␤/BMP family,WNTs,Shh,and neurotrophins)not only acti-vate morphogenesis but also regulate anagen induction and duration.27-29During anagen,epithelial stem cells differenti-ate into at least 8different cell lines,forming the ORS,com-panion layer,Henle’s layer,Huxley’s layer,cuticle of the IRS,cuticle of the hair shaft,shaft cortex,and shaft medulla.The ORS probably is established by the downward migration of the regenerating epithelium.30IRS and hair shaft are tied together by their interlocked cuticle structures.The IRS-packaged shaft uses the innermost layer of the ORS (compan-ion layer)as a slippage plane for orientation to move straight toward the skin surface.31,32Epithelial stem cells are located in the bulge area of the follicle.From there,stem cells ascend into the interfollicular epidermis and descend to differentiate into ORS cells.Onehypothesis suggests that derivatives of stem cells from the bulge area reach the hair germ,transform into matrix kera-tinocytes,and rebuild the hair shaft.33During catagen,this stem cell population is situated lateral to the DP,being secure from apoptosis and able to proliferate again in early anagen to produce a new hair shaft.Hair shaft synthesis and pigmentation only take place in anagen.The cyclic reconstruction of an intact hair follicle pigmentary unit works optimally in scalp follicles during the first 10hair cycles,meaning until approximately 40years of age.Afterward there appears to be a genetically regulated exhaustion of the pigmentary potential of each individual follicle leading to “hair greying.”34Apart from the melano-cortins,␣-MSH and ACTH and also stem cell factor,nerve growth factor (NGF),and hepatocyte factor (HGF)are in-volved in the regulation of pigmentation.35-37The anagen period ends with a highly controlled involu-tion of the hair follicle resulting in apoptosis and terminal differentiation.This process,called catagen,consists of 8dif-ferent stages.The hair follicle epithelium,neuroectodermal cell populations (melanocytes and Merkel cells),the mesen-chyme,the perifollicular vascular system,and the follicular innervation all show cyclic changes in proliferation,differen-tiation,and apoptosis.38-40The first sign of catagen is the cessation of melanin pro-duction in the hair bulb.Clinically,telogen follicles have a depigmented proximal hair shaft (club hair).Melanocytes involved in apoptosis are recruited from melanocytic stem cells of the secondary hair germ.35The programmed cell death of these stem cells might be an important factor for hair greying.41In contrast to the ORS and the hair matrix (with their huge numbers of apoptotic cells),there is no pro-grammed cell death in the DP because of the expression of the apoptosis suppressor bcl-2.38,42During catagen,the DP condenses,moves upward,and comes to rest beneath the bulge.The hairless gene (Hr)is responsible for the strong connection between the condens-ing DP and the diminishing hair follicle epithelium in catagen and telogen follicles.In its function as a safeguard of apopto-sis control during catagen 43Hr operates as a negative tran-scription repressor and insures that apoptosis only takes place in certain tissues in the correct order.The Hr gene encodes a zinc finger transcription factor whose disruption prevents the DP from ascending and interacting with stem cells of the bulge,resulting in permanent alopecia during the first catagen period.This effect also takes place in congenital atrichia with a missense mutation in the zinc-finger domain of the Hr gene.44Similarities between the phenotype of hair-less knockout mice and those with mutations of the vitamin D or RXR alpha receptor (a retinoid receptor)45suggest that Hr,vitamin D,and RXR all use the same signaling pathways to activate catagen.After regression,the hair follicle enters telogen,a phase of relative quiescence regarding proliferation and biochemical activity.The follicle remains in this stage until it is reactivated by intrafollicular and extrafollicular signals.The unpig-mented club hair often remains stuck in the hair canal.In mice,this process takes place mainly in anagen IVfollicles.Figure 2Chronobiology of the hair follicle.Every hair follicle is controlled by different timing devices.1,morphogenesis clock;2,cycling inducer;3,hair cycle clock;4,desynchronizer.The timing devices could be connected with each other and share molecular timing mechanisms (for example the hair cycle clock,which could be “set”already during morphogenesis and therefore incorporate parts of the morphogenesis clock).APM,arrector pili muscle;CTS,connective tissue sheath;DP,dermal papilla;IRS,inner root sheath;ORS,outer root sheath;SG,sebaceous gland;POD,programmed organ deletion (modified after Paus and coworkers,1999).44K.Krause and K.FoitzikThis hair cycle stage,named exogen,has its own regulations and control mechanisms.46Factors thought to participate in exogen regulation are the protease cathepsin L and Msx-2.47 To our knowledge,the hair follicle has only one irrevers-ible physiologic mechanism to break out of the hair cycle: programmed cell death.In the mouse,a few isolated hair follicles demonstrate perifollicular inflammation that de-stroys the bulge region and therefore the follicle’s capacity to cycle.48This targeted destruction probably serves to remove degenerated and nonfunctioning hair follicles.It could also play a role in forms of scarring alopecia,in the physiologic, slowly progressing loss of hair follicles in the aging human scalp,10or during thefinal stages of androgenetic alopecia.4 Locally Produced Growth Factors,Hormones,and Proteins The hair follicle is not only a very productive source of pig-mented hair shafts(keratins and melanin)but also of many growth-,pigment-,and immunomodulators.It can synthe-size or metabolize an enormous number of hormones,neu-rotransmitters,neuropeptides and growth factors.For exam-ple,growth factors like TGF-␤1/2,IGF1,HGF28,49,50and hormones like CRH,prolactin,cortisol,and melatonin51-53 are all synthesized in the hair follicle.Androgens are metab-olized to dihydrotestosterone or17␤-estradiol,and proopio-melanocortin to ACTH,alpha-MSH,or␤-endorphin within the hair follicle.2The exact biologic functions of the locally generated factors are not well understood.The hair cycle dependence of this great productive activity,as well as the expression of the specific matching receptors,suggests that these actions function as autocrine and paracrine mecha-nisms.As the hair follicle is regulated by diverse systemic extrafol-licularly generated hormones and growth factors and by a variety of self-generated substances,it is no surprise that even small changes in this sensitive milieu can lead to a shortening of anagen,an induction of catagen,and to an increased num-ber of telogen follicles,resulting in telogen effluvium. Key Factors inHair Follicle CyclingIt is now widely accepted that hair follicle transformation during cycling is caused by alterations in the local signaling milieu. There are key regulators that build up local gradients with com-peting stimulating and inhibitory signals(Fig.2).Rhythmic changes of signal transducers in the key compartments of the follicle(bulge,secondary hair germ,dermal papilla)are thought to drive cyclic hair follicle transformation.Key factors known to induce anagen include soluble pro-teins of the WNT family,activation of the corresponding ␤-Catenin pathway,noggin,and the transcription factorSTAT3.54,55Sonic hedgehog,HGF,and FGF7(KGF)support this process and stimulate the subsequent steps of anagen development.50,56,57DP-induced keratinocyte differentiation occurs via␤-catenin/lef1signaling.58Hair shaft differentia-tion seems to be mediated,at least in part,by desmoglein.59 WNT signals(WNT3a and WNT7a)are capable of keeping the dermal papilla in anagen.IGF1,HGF,glial cell-derived neurotrophic factor,and vascular endothelial growth factor can prolong anagen(Fig.3).39,47,50,54,60-64During the anagen–catagen transformation of the hair fol-licle,the transcription factor Hr is a central,indispensable element of navigation and coordination of signal transduc-tion.Loss of Hr function leads to rapid degeneration of the hair follicle.65Certain members of the homeobox gene family also seem to control some of the named factors.Msx-deficient mice,for example,show premature anagen termination,pro-longed catagen and delayed entry into the next hair cycle.47 TGF-␤1,TGF-␤2,FGF-5,the neurotrophins NT3,NT4, BDNF,p75,also retinoids,prolactin,and several other can-didates like thrombospondin1and vanilloid receptor1in-duce catagen.28,52,66-72Interestingly,there are some factors that have been shown to exert their catagen inductive activity at least in part via TGF␤2.These include retinoids,IFN-␥and BDNF.67,73,74Under the influence of BMP4and17␤-Estradiol(E2)the hair follicle stays in telogen(Fig3).74,75 An essential inhibition/disinhibition system in anagen de-velopment is the neutralization of BMP4by noggin.74Anagen is terminated by the upregulation of hair growth inhibitors (TGF-␤1,TGF-␤2,FGF-5)and downregulation of anagen preserving factors(IGF-1,HGF,FGF-5S)at the same time. The fuzzy mutation,associated with congenital atrichia,has recently been implicated in controlling both anagen and cata-gen initiation(Fig.3).76It seems confusing that some hair growth modulators have growth-stimulating effects during morphogenesis but inhib-itory effects in the hair cycle.TGF-␤2,follistatin,and NT3, for example,accelerate hair follicle morphogenesis,but are catagen-inducing in mature anagen follicles.3,27,55,77 Interestingly,many molecular hair growth manipulators also are known as key factors in wound healing(for example, members of the FGF family,EGF,IGFs,HGF,TGF-␤,VEGF, NGF,and interleukins)and as critical components in the development of teeth and feathers.78-80Some of the very potent signal transducers of anagen in-duction or termination could lead to specific pharmacologic agents that would manipulate the human hair cycle and treat hair growth disturbances more efficiently.However,none of these factors seems to be a key element of the hair cycle clock itself,which directs the factors to execute the cyclic hair follicle transformations.Sex Hormones asPotent Hair Growth Modulators Androgens are very potent,yet nonessential,hair growth modulators.In hair growth regulation,different types of hair follicles in diverse body areas have different underlying cycle control mechanisms.A common example is the paradoxical effect of androgens on terminal follicles of the scalp com-pared with vellus follicles on other parts of the body.Andro-gens stimulate hair growth in nonscalp areas like the beard,Biology of the hair follicle5breast or abdomen (at least in part by upregulation of gene expression and secretion of IGF1).49In contrast,androgen sensitive hair follicles of the scalp become smaller under the influence of androgens (miniaturization)leading to the typi-cal changes of androgenetic alopecia.10,81Inhibition of hair growth in the fronto-temporal region can be demonstrated by TGF-␤stimulation.82Current theories suggest that scalp and body hair follicles react to androgen stimulation differ-ently by triggering programmed gene regulation of defined hormones.These gene programs lead to potent hair growth stimulation in one follicle population and growth inhibition in others.80Localization and gender-specific regulation of hair follicle gene expression has also been demonstrated for estrogens.In vitro experiments show an inhibition of hair shaft elongation and anagen prolongation in human female occipital hair fol-licles,whereas in male frontotemporal scalp follicles,17␤-estradiol (E2)stimulates hair shaft elongation.75In vivo E2also leads to anagen prolongation in human hair follicles.83The role of estrogens in rodents,however,is completely dif-ferent.Topical E2induces not only premature catagen in mice,but also arrests murine hair follicles in telogen.84,85Stress and Hair LossMany patients notice increased hair loss after stress.Recently,chronic stress in mice was associated with highly significant inhibition of hair growth,increased mast cell degranulation,and perifollicular inflammation.8,86Furthermore,in vivo and in vitro studies reveal that typical stress mediators like sub-stance P,cortisol,ACTH,and prolactin inhibit hair growth.7,51,52According to Botchkarev,neural signals can modulate hair growth but are not essential for the hair cy-cle.87Human isolated hair follicles directly respond to CRH stimulation (similar to the hypothalamic-pituitary-adrenal axis)with cortisol synthesis and neuroendocrine feedback loops.51All of these data support the postulate that stress plays an important role in the development of hair loss.The Hair Cycle ClockHair transplant experiments clearly show that follicles trans-ferred from one place to another keep their original cycling behavior.2,25,88Even isolated scalp hair bulbs go through the stages of anagen–catagen transformation in vitro 60,89withoutFigure 3Molecular players in hair cycle control.The figure shows key factors of hair follicle cycling being employed by the HCC to drive the hair follicle from one stage to the next one or to keep it in a given stage.However,none of the named mediators are known to be key elements of the central pacemaker.(For references,see text,2,47,61-64).APM,arrector pili muscle;CTS,connective tissue sheath;DP,dermal papilla;IRS,inner root sheath,ORS,outer root sheath;SG,sebaceous gland;BMP,bone morphogenic protein;WNT,wingless;STAT3,signal transducer and activator of transcription 3;FGF7,fibroblast growth factor 7;HGF,hepatocyte growth factor;Shh,sonic hedgehog;IGF1,insulin like growth factor;CTSL,cathepsin L;cutl,transcriptional repressor;GDNF,glial cell line-derived neurotrophic factor;BDNF,brain-derived nerve growth factor;VEGF,vascular endothelial growth factor;ATRA,all-trans retinoid acid;RXR,retinoid x receptor;RAR,retinoid acid receptor;NGF,nerve growth factor;Lef1,lymphoid enhancer-binding protein;TGF ␤,transforming growth factor ␤;p75NTR,low affinity neurotrophin receptor;PRL,prolactin;PRLR,prolactin receptor;IFN ␥,interferon ␥;ER,estrogen receptor;IL1,interleukin 1;VR1,vanilloid receptor 1;TNF ␣,tumor necrosis factor ␣;TSP1,thrombospondin 1;(modified after Paus and Peker,2003).6K.Krause and K.Foitzikthe need for intact innervation,vascularization,or other ex-trafollicular components.These observations indicate that the basic oscillator system,which drives hair follicle cycling, is located in the skin,and likely the hair follicle itself.Based on an oscillating molecular pacemaker,this obscure hair cy-cle clock is responsible for the programmed cyclic transfor-mation of the hair follicle and its surrounding structures(Fig.2).There are differing theories about how the hair cycle clock works.In1954,Chase postulated there could be endogenous mitotic inhibitors that accumulate during anagen,finally halting the anagen phase.Because of the subsequent endog-enous mitotic inhibitors downregulation,the hair follicle is disinhibited,entering a new anagen phase.90Stenn later sug-gested an inhibition/disinhibition system that resides in the epithelial stem cell-containing bulge region as the central pacemaker.91A current hypothesis locates the hair cycle clock in the DP(linked to the cell cycle of dermalfibroblasts). During the resting time of the cell cycle(G0/G1),there could be so-called“papilla morphogens,”that stimulate matrix ker-atinocytes and follicular pigmentation(as well as suppress apoptosis).In this mode,the beginning of the cell cycle(S, G2,M)would stop the secretion of morphogens(meaning anagen would be stopped by a lack of suppression of apopto-sis)and lead to catagen transformation.While leaving the cell cycle,dermalfibroblasts would resume the secretion of mor-phogens and thereby induce a new anagen stage.19None of these speculative theories has been proven.Figure2illus-trates hair follicle morphogenesis and the hair cycle.Analo-gies in the regulation of morphogenesis and the adult hair cycle point to a connection between their underlying pace-makers.The equivalent of an inhibition/disinhibition system can be seen in the hair cycle inducer/desynchronizer system. Management of Hair Growth Disorders:Principles,CurrentOptions,and Future Prospects The majority of the known hair growth disorders are a con-sequence of changes in the hair cycle.The most frequent growth disorder in men and women is androgenetic alopecia (AGA).AGA is characterized by a shortening of the anagen phase and a prolongation of telogen,combined with minia-turization of hair follicles.10These changes are androgen de-pendent and genetically determined.The underlying molec-ular mechanism depends on the conversion of testosterone to dihydrotestosterone by5␣-reductase.Dihydrotestosterone binds to androgen receptors of the hair follicle and leads to a shortening of anagen and a reduced cell hair matrix vol-ume.92,93Men and women with AGA have a higher activity of 5␣-reductase type II and androgen receptors in the frontal scalp area compared with the occipital area.94The common opinion that miniaturization from terminal to vellus follicles is a slow process over several hair cycles has been challenged by the hypothesis of an androgen-induced emigration offibroblasts from the dermal papilla into the connective tissue sheath.A migration of this sort has been observed in mice,14and it seems plausible that androgens may influence afibroblast transfer that leads to an increase or decrease of the dermal papilla volume.Clinically visible as terminal-to-vellus or vellus-to-terminal hair follicle conver-sion,this would explain the androgen dependent genesis of alopecia or hirsutism.Whiting also suggested the concept that miniaturization is an abrupt,large-step process which can be reversed in a single cycle.In his opinion,a marked reduction of DP cells leads to a reduction of DP size,follicle size and anagen length.This theory would explain the prompt appearance of vellus hairs in some cases of AGA,the rapid regrowth of terminal follicles afterfinasteride treat-ment,and the sudden vellus-to-terminal switch of body hairs at puberty.5Figures4and5illustrates how common hair growth dis-orders can be managed by manipulating the hair cycle at different time points.AGA and telogen effluvium(caused by drugs,endocrine,and metabolic disturbances)could be treated by inhibiting premature catagen transition and/or stimulating the telogen/anagen transformation.Catagen in-duction and arrest of follicles in a prolonged telogen stage may be a therapy for hypertrichosis andhirsutism.Figure4Common hair growth disorders frequently arise from changes of the hair cycle.They can be managed by manipulating the length of the different hair cycle stages.Anagen:growth phase with active production of a pigmented hair shaft,maximal length and volume of the follicle;catagen:apoptosis-driven phase of hair cycle regression with cessation of hair shaft production and pigmentation and club hair formation;telogen:phase of relative quiescence of hair follicle activity,while the club hair rests loosely anchored in the hair canal;exogen:active shedding of club hair which usually occurs in anagen IV in mice but can also take place in telogen;hair aging: number of predetermined hair cycles in life time could be slowed down;ϩ,stimulate;Ϫ,inhibit(modified after Paus and coworkers, 1999).19Biology of the hair follicle7。

P-cadherin在‘高山美利奴羊’胚胎皮肤毛囊基板形成过程中的表达规律刘善博;岳耀敬;郭婷婷;王天翔;史兆国;袁超;王喜军;刘继刚;刘建斌【摘要】[目的]研究P-cadherin在‘高山美利奴羊’皮肤毛囊(hair follicle,HF)基板形成过程中的分布及表达情况,初步探讨P-cadherin是否可以作为‘高山美利奴’羊毛囊基板的标记物.[方法]以90-114 d胎龄的‘高山美利奴羊,腹部皮肤作为材料,通过冰冻切片、HE染色、荧光定量PCR、免疫组化技术研究P-cadherin在毛囊基板形成过程中的表达规律.[结果]免疫组化结果显示,P-cadherin在胚胎毛囊形成时期的表皮、表皮基底层、真皮、隆突基底层、基板以及毛芽中都呈现阳性表达.荧光定量结果显示,在胎龄90、96、102、108、114 d的相对表达量分别为(0.016 7±0.008 4)(0.113 4±0.052 9)(0.937 8±0.245 3)(0.068 4±0.0268)(0.062 3士0.045 6).90 d与96 d相比差异显著(P=0.049 3＜0.05),96 d与102 d相比差异不显著(P=0.088 9＞0.05),102 d与108 d相比差异显著(P=0.023 5＜0.05),108 d与114 d相比差异不显著(P=0.512 4＞0.05).96 d以后的相对表达量高于90 d的相对表达量.90d到102 d相对表达量逐渐升高,102 d以后相对表达量逐渐降低,108 d以后相对表达量趋于平稳,但是略高于114 d的相对表达量,有降低的趋势.[结论]初步可以断定P-cadherin可以作为‘高山美利奴羊’毛囊基板的标记物.【期刊名称】《甘肃农业大学学报》【年(卷),期】2016(051)005【总页数】6页(P1-6)【关键词】甘肃‘高山美利奴羊’;毛囊基板;P-cadherin【作者】刘善博;岳耀敬;郭婷婷;王天翔;史兆国;袁超;王喜军;刘继刚;刘建斌【作者单位】甘肃农业大学动物科学技术学院,甘肃兰州730070;甘肃农业大学动物科学技术学院,甘肃兰州730070;中国农业科学院羊育种工程中心,中国农业科学院兰州畜牧与兽药研究所,甘肃兰州 730050;中国农业科学院羊育种工程中心,中国农业科学院兰州畜牧与兽药研究所,甘肃兰州 730050;甘肃省绵羊繁育技术推广站,甘肃张掖734031;甘肃农业大学动物科学技术学院,甘肃兰州730070;中国农业科学院羊育种工程中心,中国农业科学院兰州畜牧与兽药研究所,甘肃兰州 730050;甘肃省绵羊繁育技术推广站,甘肃张掖734031;甘肃省绵羊繁育技术推广站,甘肃张掖734031;中国农业科学院羊育种工程中心,中国农业科学院兰州畜牧与兽药研究所,甘肃兰州 730050【正文语种】中文【中图分类】S826.9+1影响细毛羊经济效益的主要性状有羊毛的产量、细度、净毛率等，这些性状中产毛量与毛囊的(hair follicle,HF)发育有直接的关系.毛囊是控制毛绒生长的器官.‘高山美利奴羊’次级毛囊形态发生时期已经被确定[1-4].毛囊形态发生开始于基板(placode，P)的形成，基板是间叶细胞凝集于排列整齐的表皮细胞下方形成的一种特殊结构，这些特定的结构之间的相互作用进一步引起基板的生长[5].基板作为毛囊发育的前体器官，其形成过程涉及一系列复杂的表皮和真皮之间的信号通路.目前在毛囊基板形态发生分子机制的研究中，多以多种类型组织(真皮、表皮、毛囊等)混合的皮肤做为起始样本，并未分离出匀质性基板组织，这使得调控基板发生的关键基因生物差异有可能被平均值所掩盖或是被误认做为技术噪音[6]，亟需寻找一种基板细胞标志物，以高效分离基板细胞进行基板单细胞功能基因组研究. 目前，P-cadherin常用于人和鼠等毛囊基板形态发生研究中的标志物.P-cadherin 属于钙粘素(Cadherin)家族里面的一种，由CDH3编码，其表达受Wnt/β-catenin信号通路的调节.研究结果表明，HF从原始表皮开始进行初始分化时Wnt 信号能够促进β-catenin的产生.当胚胎表皮细胞重新定位形成上皮芽胞随后形成成熟的HF时β-catenin/LEF1转录复合物会使E-cadherin的表达量减少.因此，在这个关键时期，间质细胞上皮界面主要含有的是P-cadherin，作为毛发的前体细胞[7-8].目前对于P-cadherin在哺乳动物组织尤其是在人类和小鼠毛囊里面的分布和表达情况已经有了比较深入的研究.其某些表达特性与报道的关于毛囊和表皮标记物的特性有些相似.研究证明，其永恒存在于小鼠表皮，并且在外根鞘(ORS)以及最接近真皮乳头的毛母质细胞(HMCs)和次级毛芽(KCs)中表达[8].有报道显示，P-cadherin在7-8周人类胚胎皮肤中基底层细胞中有表达，但是在上皮细胞中不表达[9].此外，在人类医学的相关研究中证明P-cadhrin与脱发、秃发和多毛症等毛发疾病密切相关[10-11].研究显示，在人类毛囊发育过程中，P-cadhrin是唯一一个在内部毛母质细胞(IHM)表达的钙粘蛋白[8].但P-cadhrin是否是‘高山美利奴羊’毛囊基板的标记物还需进一步研究.因此，本研究通过实时荧光定量PCR技术和免疫组化技术，研究‘高山美利奴羊’胎儿皮肤HF形态形成过程中基板形成时期P-cadhrin在mRNA水平和蛋白水平的表达情况，初步研究P-cadhrin在‘高山美利奴羊’毛囊基板形态发生中的调控作用，以期为阐明P-cadhrin能否作为‘高山美利奴羊’毛囊基板形态发生调控中的标记物和研究绵羊HF基板形成的分子调控机制研究提供试验数据和理论依据.1.1 试验材料在甘肃省绵羊繁育技术推广站(原甘肃省皇城绵羊繁育试验场)选择体格均匀的经产2～3岁‘高山美利奴母羊’15只，用同一只种公羊进行人工授精，以人工授精日为第0日，分别于胚胎90、96、102、108、114 d日龄剖取胎儿，每次3只，在其体侧部切取2 cm2的皮肤.0.9%生理盐水冲洗处理后装入冻存管，迅速投入液氮中保存备用.1.2 试剂和仪器冰冻切片机(Leica 9500)、显微镜(Leica DM5500)，二甲苯、无水乙醇、冰醋酸、甲醇、多聚甲醛、中性树脂、30%蔗糖溶液、30% H2O2、苏木素、伊红、OCT包埋剂，DAB显色剂，1%PBS溶液等试剂均购自福建迈新公司.一抗：P-cadherin SABC即用型试剂盒(BA0674)、二抗：IgG(SA1029)均购自武汉博士德生物工程公司.TRNzol总RNA提取试剂盒(DP405)、Quant One Step RT-PCRkit(KR113)、SuperReal PreMix (SYBR Green)(FP204)购自天根生化科技(北京)有限公司.1.3 试验方法1.3.1 样品处理首先，将新鲜的皮肤组织样在4%多聚甲醛中固定24 h后放在30%的蔗糖溶液中过夜.其次，用梯度酒精脱水.最后，对处理好的组织块进行修块和包埋.1.3.2 HE染色对90、96 d的组织进行冰冻切片，寻找基板形成时期的不同形态.将冰冻切片机在-25 ℃提前预冷24 h后对包埋好的组织块进行切片，切片厚度为10 μm，贴片；将贴好的切片自然晾干，在4%多聚甲醛中浸泡30 min进行固定；用PBS冲洗后进行苏木素轻度染色.1.3.3 免疫组化将冰冻切片机在-25 ℃提前预冷24 h后对包埋好的组织块进行切片，切片厚度为8 μm，贴片；将贴好的切片自然晾干，在4%多聚甲醛中浸泡30 min进行固定；在30% H2O2+纯甲醇50份混合的溶液中室温浸泡30 min(此步的目的是将内源性过氧化物酶进行灭活)，用超纯水洗1-2次；滴加5% BSA封闭液，室温孵育20 min，将多余的封闭液甩去，此步不洗；滴加(1∶75)稀释浓度的小鼠一抗，37 ℃孵育3 h.PBS洗3次，2 min/次；滴加生物素标记的抗小鼠IgG，37 ℃孵育20 min，PBS洗3次，2 min/次；加SABC试剂，37 ℃孵育20 min，PBS洗4次，5 min/次；进行DAB显色，室温下显色5 min；苏木素轻度复染约10 s，蒸馏水冲洗2～3 min；梯度酒精脱水、透明、封片、微镜下观察实验结果、拍片.1.3.4 实时荧光定量PCR(RT-PCR) 根据GeneBank中公布的绵羊的P-cadherin的mRNA序列(XM-012095002.1)，利用TaKaRa专用引物设计软件设计特异性引物，引物合成由TaKaRa公司合成.目的基因的名称、序列信息及退火温度等见表1.采用TRIZOL法对‘高山美利奴羊’胚胎皮肤组织进行总的RNA的提取.参照Quant One Step RT-PCR 试剂盒、SuperReal PreMix Plus (SYBR Green)试剂盒说明进行定量PCR反应.实时荧光定量PCR对样品的cDNA和阴性对照进行扩增，内标基因为GAPDH.反应体系为10 μL，其中灭菌去离子水4 μL,SuperReal PreMix Plus (2.5×Real PreMix Plus，20× SYBR Green solution ) 5 μL，上下游引物各0.2 μL(终浓度5 pM),cDNA 样品0.6 μL.整个反应在Bio-Rad Real-Time CFXTM96 System中进行，每个样品及内标基因各做3个重复.反应程序为：95 ℃ 3min，95 ℃ 30 s，60 ℃ 30s，72 ℃ 30 s，40个循环.基因的相对表达量采用2-ΔΔCT法计算[12].然后用SPSS软件进行统计分析，P-cadherin相对表达量结果均表示.1.4 数据分析基因的相对表达量采用2-ΔΔCT法计算[12].然后用SPSS 19.0软件进行统计分析，并用F检验和Duncan法进行多重比较.P-cadherin相对表达量结果均以±s表示.2.1 HE染色及免疫组化结果基板是由间质细胞排列在表皮细胞的下方形成的一种特殊结构，其形成大概分为4个时期：真核细胞在表皮下方均匀排列(图1-A)；真核细胞逐渐聚集于表皮下方(图1-B)；真核细胞继续聚集形成隆突(图1-C)；形成基板(图1-D).免疫组化结果显示P-cadherin在基板形态发生中都有表达.其主要是在表皮(图2-A-a)、真皮(图2-A-b)、表皮中间层(图2-B-a)、表皮基底层(图2-B-b)、隆突底部(图2-C-b)、基板(图2-D-b)中表达.2.2 荧光定量结果对荧光定量数据进行SPSS分析，结果显示：在胎龄90、96、102、108、114 d 的相对表达量分别为(0.016 7±0.008 4)(0.113 4±0.052 9)(0.937 8±0.2453)(0.068 4±0.026 8)(0.062 3±0.045 6).90 d与96 d相比差异显著(P=0.0493<0.05)，96 d与102 d相比差异不显著(P=0.088 9>0.05)，102 d与108 d相比差异显著(P=0.023 5<0.05)，108 d与114 d相比差异不显著(P=0.5124>0.05).96 d以后的相对表达量都要高于90 d的相对表达量(图3).90 d到102 d 相对表达量逐渐升高，102 d以后相对表达量逐渐降低，108 d以后相对表达量趋于平稳，但是略高于114 d的相对表达量，有降低的趋势.本研究通过对‘高山美利奴羊’腹部皮肤进行定点、定量的研究，发现P-cadherin在‘高山美利奴羊’毛囊基板形态发育时期的表皮、真皮、隆突区、隆突基底层、基板和毛钉中都有表达.这与之前报道的在P-cadhrin小鼠表皮组织里面有表达并且是持续表达相符合[13].从荧光定量的结果可以看出从表皮细胞开始聚集到基板形成时期P-cadhrin 96 d以后P-adherin的表达量逐渐降低，这与之前所报道的在人类毛发生长周期中期P-cadherin的表达呈现逐渐减弱的趋势相一致[14]，证明P-cadherin在表皮终末分化过程中发挥着重要的作用[15].另外，本试验结果中基板形成时期P-adherin的相对表达量(图2)都要明显高于表皮中的表达量(图2)，这与报道的人类基板中的表达量明显高于表皮中的表达量相一致[7]. 目前，已经报道的一些关于毛囊干细胞和表皮干细胞的标记物具有一定的特征：1) 在细胞中所处的位置不同：位于细胞膜的有整合素、CD34、CD200和ABCG2(转运蛋白超蛋白家族)等；位于细胞质的有角蛋白和巢蛋白等；位于细胞核的有p63、Tcf3(人类T细胞因子)、Lgr5、Lhx2、Sox9和NFATc1(活化T细胞核因子1)等[16].2) 特定的表达部位：ABCG2集中表达于表皮基底层和毛囊隆突区[17].Sox9集中表达于毛囊的外根鞘[18].CK14在云南半细毛羊毛囊干细胞中表达，在成纤维细胞中则不表达[19].p63在角膜缘的基底细胞表达但是在角膜表面的短暂增殖细胞则不表达[20].3) 特定的表达种属：CD34只在小鼠毛囊中表达，但不在人类中表达[21].4) 不同时期或者不同部位表达量不同：β1整合素在ESCs细胞表面高度表达，但是在细胞有丝分裂后却不表达[22].从本试验免疫组化结果可以看出在绵羊毛囊基板形成时P-cadherin有一定的表达部位，其集中在表皮、表皮基底层、隆突基底层和基板基底层表达.从荧光定量结果可以看出P-cadherin在毛囊发育的不同时期表达量不同：从90 d间叶细胞开始聚集到96 d基板和毛芽形成，相对表达量显著增加；从102 d初级毛囊产生到108 d形成再分化次级毛囊一直到114 d次级毛囊产生相对表达量逐渐降低，108 d和114 d趋于平稳，但是仍然低于96 d.因此，可以初步断定P-cadherin可以作为‘高山美利奴羊’毛囊基板的标记物.本研究对P-cadherin在‘高山美利奴羊’毛囊基板形态发生过程中的表达变化规律进行了初步研究，得出P-cadherin参与‘高山美利奴羊’毛囊基板形态发生的调控，并且可以初步断定P-cadherin可以作为‘高山美利奴羊’毛囊基板的标记物.【相关文献】[1] Rogers G E.Biology of the wool follicle:an excursion into a unique tissue interaction system waiting to be re-discovered[J].Exp Dermatol，2006,15(12):931-949[2] 吴瑜瑜，岳耀敬，郭婷婷，等.中国超细毛羊(甘肃型)胎儿皮肤毛囊发育及其形态结构[J].中国农业科学，2013，46(9)：1923-1931[3] Galbraith H.Fundamental hair follicle biology and fine fibre production inanimals[J].Animal，2010,4(9):1490-1509[4] 赵帅，岳耀敬，郭婷婷，等.Wnt 10 b、β-catennin、FGF18基因在‘甘肃高山细毛羊’胎儿皮肤毛囊中的表达规律研究[J].甘肃农业大学学报，2015，50(5)：6-14[5] Schmidt-Ullrich R.Paus R.Molecular principles of hair follicle induction and morphogenesis[J].Bio Essays，2005(27):247-261[6] Liu G,Liu R,Li Q,Tang X,et al.Identification of microRNAs in wool follicles during anagen,catagen,and telogen phases in Tibetan sheep[J].PloS One，2013,8(10):e77801 [7] Jamora C,Das 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头发和头皮护理的科学基础涉及到生物学、化学和皮肤学等多个领域。

以下是头发和头皮护理的一些科学基础：
1.头发结构：头发主要由蛋白质（角蛋白）组成，这些蛋白质通过氢键和硫醚键相互连
接形成螺旋结构。

这种螺旋结构赋予了头发强度和弹性。

2.头皮生理：头皮是头发的生长基底，也是汗腺和毛囊的位置。

头皮的健康对头发的生
长和质量非常重要。

头皮的皮脂腺分泌皮脂，这有助于保持头皮的水分平衡。

3.洗发和护发产品：洗发和护发产品通常包含清洁剂、保湿剂、营养成分等。

清洁剂可
以去除头发上的污垢和油脂，但过度清洁可能导致头皮干燥。

保湿剂有助于保持头发和头皮的水分。

营养成分如维生素、氨基酸和蛋白质可以提供营养，促进头发的健康生长。

4.pH 值：头皮和头发的pH 值对其健康起着重要作用。

过于碱性或酸性的洗发产品可
能破坏头发的结构和头皮的平衡。

5.头皮问题：一些头皮问题如头屑、瘙痒和头皮屑等可能与真菌感染、皮肤炎症等有关。

科学合理的护理可以有助于减轻这些问题。

6.防晒和保护：头发也需要防晒和保护。

紫外线和环境污染可能损害头发的结构和颜色。

7.生活方式和饮食：良好的生活方式和均衡的饮食对头发和头皮健康同样重要。

足够的
水分、蛋白质、维生素和矿物质对头发的健康有积极影响。

综上所述，头发和头皮护理的科学基础涉及多个领域，从头发结构到化学成分，再到生理和环境因素。

理解这些基础知识可以帮助你选择适合自己头发类型和需求的护理方法和产品。

头发生长的过程作文英语The Process of Hair Growth。

Hair growth is a natural process that occurs in all humans and animals. It is a complex process that involves different stages and factors. In this essay, we will explore the process of hair growth and the factors that affect it.The first stage of hair growth is the anagen phase. This is the active growth phase of the hair follicle, where the hair grows from the root. During this phase, the hair follicle is nourished by blood vessels, which provide the necessary nutrients for hair growth. The anagen phase can last for several years, depending on the individual's genetics and other factors.The second stage of hair growth is the catagen phase. This is a transitional phase where the hair stops growing and detaches from the blood supply. The hair follicleshrinks and the hair shaft is pushed up towards the surface of the skin. The catagen phase lasts for a few weeks.The final stage of hair growth is the telogen phase. This is the resting phase where the hair follicle is inactive and the hair is no longer growing. The hair remains in this phase for a few months before it falls out and the cycle starts again.There are several factors that can affect the process of hair growth. Genetics play a significant role in determining the length and thickness of hair. Hormones, such as testosterone and estrogen, also play a role in hair growth. Stress, diet, and environmental factors can also impact hair growth.To promote healthy hair growth, it is important to maintain a balanced diet that includes protein, vitamins, and minerals. Regular exercise can also improve blood circulation, which can help to nourish the hair follicles. Avoiding harsh chemicals and heat styling tools can also help to prevent damage to the hair.In conclusion, hair growth is a natural process that involves different stages and factors. Understanding the process of hair growth and the factors that affect it can help to promote healthy hair growth. By maintaining a balanced diet, exercising regularly, and avoiding harsh chemicals and heat styling tools, we can help to keep our hair healthy and strong.。

关于科学护肤的作文标题英文回答：Title: The Science of Skincare.Skincare has always been a topic of interest for many people, and with the advancements in science, it has become even more fascinating. The science of skincare involves understanding how our skin works and finding ways to maintain its health and appearance. In this essay, I will explore the science behind skincare and discuss its importance in our daily lives.One of the key aspects of scientific skincare is understanding the structure and function of our skin. Our skin is the largest organ of our body and serves as a protective barrier against external factors. It consists of three main layers: the epidermis, dermis, and hypodermis. Each layer has its own unique role in maintaining the health and integrity of our skin.The epidermis, the outermost layer of our skin, acts as a waterproof barrier and protects us from harmful substances. It is composed of different types of cells, including keratinocytes, which produce a protein called keratin that gives our skin its strength and elasticity. The dermis, located beneath the epidermis, contains blood vessels, hair follicles, and sweat glands. It provides support and nourishment to the epidermis. Finally, the hypodermis, also known as the subcutaneous tissue, is made up of fat cells that help insulate our body and regulateits temperature.Understanding the structure of our skin is crucial in developing effective skincare products. For example, moisturizers are designed to penetrate the epidermis and hydrate the skin from within. They contain ingredients such as hyaluronic acid, which can hold up to 1000 times its weight in water, thus providing long-lasting hydration. Another example is sunscreen, which works by forming a protective layer on the skin's surface to shield it from harmful UV rays.In addition to understanding the structure of our skin, scientific skincare also involves studying the various factors that can affect its health and appearance. These factors include genetics, lifestyle choices, and environmental factors. For instance, certain geneticfactors can predispose individuals to skin conditions such as acne or eczema. Lifestyle choices, such as smoking or excessive sun exposure, can accelerate the aging process and lead to premature wrinkles and sunspots. Environmental factors, such as pollution and harsh weather conditions, can also damage our skin and compromise its health.To address these concerns, scientists have developed a wide range of skincare products that target specific skin issues. For example, acne treatments often contain ingredients like salicylic acid or benzoyl peroxide, which can help unclog pores and reduce inflammation. Anti-aging products, on the other hand, may contain retinol or peptides, which can stimulate collagen production and improve skin elasticity.In conclusion, the science of skincare plays a crucial role in maintaining the health and appearance of our skin. By understanding the structure and function of our skin, as well as the factors that can affect its health, scientists have been able to develop effective skincare products that cater to our specific needs. Whether it's moisturizers, sunscreens, or anti-aging treatments, scientific skincare offers a wealth of options to help us achieve and maintain healthy, radiant skin.中文回答：标题，科学护肤的奥秘。