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雅思16 阅读passage2The passage discusses the issue of food waste and its impact on the environment. It highlights the significant amount of food that is wasted globally and the negative consequences of this wastage. The passage also explores the reasons behind food waste and suggests potential solutionsto address this issue.From an environmental perspective, food wastecontributes to various environmental problems. When food is wasted, the resources used to produce that food, such as water, energy, and land, are also wasted. This not only leads to a significant loss of resources but alsocontributes to environmental degradation. Food waste also results in the release of greenhouse gases, such as methane, as the wasted food decomposes in landfills. These gases contribute to climate change and further exacerbate environmental issues. Therefore, reducing food waste is crucial for mitigating the environmental impact of food production and consumption.From a social perspective, food waste has ethical implications. In a world where millions of people suffer from hunger and malnutrition, wasting a large amount of food is morally unacceptable. Food waste represents a significant missed opportunity to address food insecurity and hunger. By reducing food waste, it is possible to redirect surplus food to those in need, therebycontributing to the alleviation of hunger and poverty. Additionally, reducing food waste can also help lower food prices, making food more affordable and accessible to a larger population.From an economic perspective, food waste represents a loss of resources and money. The resources used to produce food that is ultimately wasted represent a significant financial investment. Furthermore, businesses and consumers incur financial losses when food is wasted. For businesses, food waste leads to lost revenue and increased operating costs for waste disposal. For consumers, wasting food means wasting money spent on purchasing that food. Therefore, reducing food waste is not only environmentally andsocially beneficial but also economically advantageous.From a cultural perspective, food waste reflects a disconnect between food production and consumption. In many societies, there is a culture of abundance and excess, leading to a lack of appreciation for the value of food. This culture of excess has contributed to the normalization of food waste. Changing cultural attitudes towards food and promoting a greater appreciation for the resources and effort required to produce food is essential for addressing food waste. By fostering a culture of mindfulness and respect for food, it is possible to reduce food waste and promote more sustainable food consumption practices.From a personal perspective, individuals play a crucial role in addressing food waste. By being mindful of their food consumption habits, individuals can significantly reduce food waste at the household level. This includes proper meal planning, storing food correctly, and being conscious of portion sizes. Additionally, individuals can support initiatives and organizations that work towards reducing food waste, such as food banks and community foodredistribution programs. By taking personal responsibility and actively participating in efforts to reduce food waste, individuals can contribute to positive change and make a difference in addressing this critical issue.。
Notch信号转导通路与肿瘤的关系[摘要]Notch信号通路是一个既简单而又复杂的信号通路，且在多个物种中表达。
Notch 信号通路与细胞的分化、增殖、凋亡、黏附及表皮细胞向间充质细胞的转化有密切联系。
Notch通路在不同的肿瘤中，起不同的作用，也可能在肿瘤的不同发展阶段展现不同的作用。
本文就Notch在肿瘤研究中的研究进展作以综述。
[关键词] Notch；信号通路；肿瘤[Abstract] Notch pathway is a complex and easy pathway. It was expressed in many species. Notch pathway was associated with cellular differentiation, proliferation, apoptosis and adherency.Notch pathway plays a different part in different tumors. The research progress of Notch pathway in tumor study was reviewed.[Key words]Notch; pathway; tumor20 世纪80 年代中期一种可引起果蝇翅膀残缺的跨膜受体基因被克隆出来，并被命名为Notch受体。
研究发现包括哺乳动物在内的很多生物都能表达这种受体，Notch信号通路与细胞的分化、增殖、凋亡、黏附及表皮细胞向间充质细胞的转化有密切联系，人类对肿瘤的研究打开了一个新的窗口[5]。
Notch信号转导通路对于细胞的生长发育具有广泛影响, 主要是通过调控细胞的分化、增殖和凋亡影响正常生长。
Notch信号通路与其他肿瘤发生、发展的关键性通路相互作用。
其与肿瘤的相关性最先在由点突变或染色体易位引起的T细胞白血病中确立。
随着研究的深入，大量实验证明Notch信号通路的活性变化与其他肿瘤的发生、发展也有密切的关系，如皮肤癌、肝癌、脑肿瘤和乳腺癌等。
1602022年1月上 第01期 总第373期学术研究China Science & Technology Overview黄曲霉毒素（Afl atoxin, AFT）主要由黄曲霉和寄生曲霉产生，有极强的毒性和致癌性，以黄曲霉素B1（Afl atoxin B1, AFB1）最为多见[1]，能够造成肝脏、肾脏、胃肠道等器官不同程度的损伤[2]。
AFB1被世界卫生组织（WorldHealth Organization, WHO）和国际癌症研究机构（Inter-national Agency for Research on Cancer , IARC）列为Ⅰ类致癌物[3]。
近年来，黄曲霉毒素因其较强的毒性效应及其对人畜健康的强烈危害性而引起人们的广泛关注和研究。
1.黄曲霉毒素的分子结构和理化性质AFT 是一种主要由曲霉属中的黄曲霉和寄生曲霉所产生的有毒次生代谢产物[4]，其基本结构为1个二呋喃环和1个氧杂萘邻酮（香豆素）组成（见图1），是一类化学结构相类似的二呋喃香豆素衍生物[5]，耐高温、强酸，极难分解[6]。
目前已发现黄曲霉素B 1、B 2、G 1、G 2、M 1、M 2等20余种异构体[7]。
它们的区别在于，经紫外线照射后，B 族发蓝紫色荧光，G 族发绿色荧光，其中B 1最为常见，且毒性最强[5]。
由细胞色素P450 1A2（CYP1A2）作用产生的AFM1是AFB 1的主要羟基化代谢产物，AFB 1微溶于水，不溶于非极性溶剂，可溶于极性有机溶剂，且稳定性较强、耐热[8]。
2.黄曲霉毒素的毒性效应2.1 黄曲霉毒素对生物大分子的影响黄曲霉毒素和其进入机体后形成的复合物能够抑制细胞中DNA、RNA 和蛋白质等物质的合成，从而影响机体的正常代谢和遗传物质的复制[9]。
Zhao 等[10]研究发现AFB 1可以使L02细胞的DNA 甲基化，并在miRNA 的调控下诱导细胞恶性转化从而引发癌症。
2.2 致癌、致畸、致突变性AFT 具有致癌性，AFB1慢性暴露会造成肝脏、肾脏和胃等器官的损伤并引发癌变[8]，并且AFT 诱发的癌变往往与突变相关[11]。
Vol.41No.2Feb.2021上海交通大学学报（医学版）JOURNAL OF SHANGHAI JIAO TONG UNIVERSITY (MEDICAL SCIENCE)黄芩苷抗肿瘤作用机制的研究进展刘梦珂，纪濛濛，程林，黄金艳，孙晓建，赵维莅，王黎上海交通大学医学院附属瑞金医院血液科，上海市血液学研究所，医学基因组学国家重点实验室，国家转化医学研究中心，上海200025［摘要］黄芩苷是从中药黄芩中提取出来的一种黄酮类化合物。
研究表明其作为黄芩的有效成分之一，在抗氧化、抗炎症和抗病毒等方面均具有疗效。
随着研究的深入，黄芩苷在抗肿瘤方面的作用被逐渐地认识，其对肿瘤的影响和抗肿瘤的作用机制，如阻滞肿瘤细胞周期、诱导肿瘤细胞凋亡、防治肿瘤转移和调节肿瘤微环境等，使其成为中药抗肿瘤研究的新热点。
该文对黄芩苷抗肿瘤作用的研究现状进行综述，以期增进对其抗肿瘤机制的认识，为肿瘤治疗提供新的思路。
［关键词］黄芩苷；抗肿瘤；肿瘤凋亡；肿瘤转移；肿瘤微环境［DOI ］10.3969/j.issn.1674-8115.2021.02.019［中图分类号］R285.6［文献标志码］AResearch progress in anti-tumor effect and mechanism of baicalinLIU Meng -ke,JI Meng -meng,CHENG Lin,HUANG Jin -yan,SUN Xiao -jian,ZHAO Wei -li,WANG LiDepartment of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine;Shanghai Institute of Hematology;State Key Laboratory of Medical Genomics;National Research Center for Translational Medicine,Shanghai 200025,China[Abstract ]Baicalin is one of the flavonoids extracted from the root of Chinese herb Scutellaria baicalensis ,which is proved to be an effective component in fields of anti-oxidant,anti-inflammation and anti-virus.Based on further studies,baicalin is gradually known to have anti-tumor function.It has an impact on tumor via multiple mechanisms such as induction of tumor cell cycle arrest,induction of apoptosis of tumor cell,inhibition of tumor metastasis and regulation of tumor microenvironment,ranking it a hotspot in Chinese medicine of anti-tumor therapy.This article comprehensively reviews the previous studies on the anti-tumor effect of baicalin,in order to promote understanding of its anti-tumor mechanisms and provide a new insight in anti-tumor therapy.[Key words ]baicalin;anti-tumor;tumor apoptosis;tumor metastasis;tumor microenvironment传统中药治疗肿瘤的研究已引起广泛的关注。
2012年12月第9卷第34期·综述·CHINA MEDICAL HERALD 中国医药导报神经再生研究给神经科疑难病的治疗带来了新的机遇。
基于神经干细胞的治疗策略可分为两类，一是原位激活内源性的神经干细胞或前体细胞达到神经再生的目的，二是将体外扩增的神经干细胞或前体细胞植入到受损的中枢神经系统，即细胞替代治疗。
神经干细胞的增殖、分化及迁移受内因（基因调控）和外因（细胞微环境）的共同影响。
本文主要阐述内源性神经干细胞的原位激活及其诱导微环境，为神经干细胞应用于临床提供理论依据。
1内源性神经干细胞的特性1.1内源性神经干细胞的存在部位大量研究证实，成体神经系统内存在神经干细胞，这些来源于受体自身的干细胞称为内源性干细胞。
在许多成年哺乳动物的海马齿状回的颗粒下层和侧脑室的室下区，始终存在神经发生。
这些神经前体细胞可增殖、分化并整合入神经回路[1-2]。
1.2内源性神经干细胞标记蛋白神经发生可分为增殖、迁移和分化三个阶段。
增生的早期标志物主要有5-溴-2-脱氧尿嘧啶核苷（5-bromo-2-de -oxyuridine ，5-BrdU ）、Nestin 等。
BrdU 是一种胸腺脱氧核苷类似物，当细胞处于DNA 合成期而同时又有BrdU 存在时，就会有BrdU 掺入新合成的DNA 中，因而视为细胞增殖的标志。
Nestin 是神经上皮前体细胞中的一种中间丝蛋白，属于细胞骨架的一种，其表达始于神经胚形成时，用于标记早期原始神经细胞。
与神经元前体细胞的迁移相关的标志物主要有多聚唾液酸神经细胞黏附因子（polysialylated neural cell adhesion molecule ，PSA-NCAM ）、Doublecortin （DCX ）等。
PSA-NCAM 的表达与神经元的迁移和神经元回路的形成有关，以介导细胞间的黏附和识别，可作为神经可塑性的标志物；DCX 内存在进化保守的重复序列，构成微管结合域，以维持微管的稳定性，可用来研究神经元前体细胞的增殖和迁移。
Notch信号通路在肿瘤中的研究进展李钰泉;周天骏;潘越江;张惠忠【摘要】Notch信号通路是一条影响细胞命运、保守而重要的信号转导通路,几乎涉及所有细胞的生长活动,在调节细胞分化、增殖和凋亡,及在一系列生理、病理过程中都起着关键性的作用,并在肿瘤的发生、发展中也发挥了至关重要的作用.近年对Notch信号通路的研究不断加深和完善,使其与肿瘤的密切关系得到了充分呈现,并有望针对相关靶点设计靶向药物,为肿瘤治疗提供新方向.【期刊名称】《岭南现代临床外科》【年(卷),期】2013(013)005【总页数】4页(P455-458)【关键词】Notch信号通路;肿瘤;靶向治疗【作者】李钰泉;周天骏;潘越江;张惠忠【作者单位】510120 广州,中山大学孙逸仙纪念医院胸外科;510120 广州,中山大学孙逸仙纪念医院胸外科;510120 广州,中山大学孙逸仙纪念医院胸外科;510120 广州,中山大学孙逸仙纪念医院胸外科【正文语种】中文【中图分类】R602Notch基因最早于1919年在Thomas Hunt Morgan等研究果蝇残翅时发现，因其功能部分缺失会在果蝇翅膀的边缘造成切迹而命名。
Notch受体是一个进化上高度保守的跨膜受体家族，从无脊椎动物到哺乳动物均有表达，其在胚胎的发育和细胞的增殖、分化，以及细胞命运的决定中起着关键性的作用［1］。
近年来，大量研究证实Notch信号通路与肿瘤的发生、发展有密切关系［2］。
1 Notch信号通路的激活及作用机制Notch信号通路由 Notch受体、Notch配体、DNA结合蛋白、细胞内效应分子和Notch的调节分子等构成［1］。
Notch受体是一个进化上高度保守的跨膜受体家族，哺乳动物有4种 Notch 受体（Notch1－4）和 5 种 Notch 配体（Delta－like 1，3，4，Jagged1和 Jagged2）。
Notch信号通路的激活需要经过三次裂解［3］（图1）。
外泌体在风湿病中作用的研究进展作者：郭晓萱李大可来源：《风湿病与关节炎》2023年第10期【摘要】外泌体是一种纳米囊泡，不同类型的细胞均可以释放，在正常情况下可以从血液、尿液等多种体液中分离得到。
外泌体及其组成成分在细胞间通讯中起着重要作用。
现如今越来越多的研究已经证实，外泌体可以将其所含成分转移到受体细胞中，从而改变受体细胞的生物活性，与各种风湿病的病理生理过程有关，并在疾病治疗和诊断中有着潜在作用。
【关键词】风湿病；外泌体；微小RNA；研究进展；综述外泌体是一种直径为30～120 nm的由磷脂双分子层膜包裹的囊泡，可以参与细胞间的信息传递［1］。
外泌体的成分包括DNA、RNA、蛋白质及脂质物质，其中微小RNA （miRNA）是一种长度为21～23个核苷酸的单链非编码小分子RNA，在人体中通过转录后抑制蛋白质编码基因的表达参与多种生物学途径的调节［2］。
长链非编码RNA（lncRNA）是一类长度超过200个核苷酸的非编码RNA，与多种自身免疫性疾病的发生、发展有关。
近期的研究表明，外泌体或许可以作为疾病诊断和预后的新生物标志物，并为多种疾病提供新的治疗方向。
1 外泌体与类风湿关节炎（rheumatoid arthritis，RA）在RA的病理过程中，外泌体主要参与抗原呈递、炎性细胞因子和miRNA的传递以及成纤维样滑膜细胞（FLS）的激活［3］。
RA患者滑膜外泌体具有较高的破骨潜能，这可能导致了其特征性的骨质侵蚀［4］。
FLS来源的外泌体可显著诱导T细胞分化，使辅助性T细胞（Th17）增加，调节性T细胞（Treg）细胞减少，通过调节Treg/Th17平衡影响RA临床症状，因此，可以作为RA的潜在治疗靶点［5］。
程明等［6］实验发现，人骨髓间充质干细胞（hBMSCs）来源外泌体miRNA-320a对CXC趋化因子配体9有负调控作用，从而抑制RA-FLS增殖和迁移能力。
外泌体来源的miR-155可能通过对趋化因子的调节而促进炎性细胞在RA滑膜中的募集和滞留，进而参与RA的发病［7］。
耳发育相关基因表达减少；特别重要的是，出现外毛细胞的缺失数目多，内毛细胞缺失数目少。
同样，体外组织培养和诱导分化的体系中，也发现敲除STAT3后出现毛细胞发育障碍。
另一方面，通过对内耳支持细胞（干细胞）有丝分裂过程分析，抑制STAT3信号通路可降低通过有丝分裂途径产生的毛细胞，进一步分析，在体外诱导毛细胞分化体系中，支持细胞通过对称与不对称分裂模式产生子代细胞。
而抑制STAT3信号通路可降低不对称分裂比例，造成毛细胞数量减少。
在第二章中，我们研究了STAT3和Notch信号通路在内耳毛细胞发育中的相互作用及功能。
通过Sox2-CreER诱导的Notch1敲除小鼠模型及组织培养，STA T3及STAT3 pS727表达在再生的毛细胞上，且STAT3表达上调，说明STAT3是由抑制Notch再生毛细胞过程的参与分子。
组织培养及体外诱导体系中，同时抑制Notch和STAT3信号通路时，与单独抑制Notch信号通路相比，毛细胞数量降低。
更重要的是，抑制Notch信号，干细胞通过不对称分裂产生毛细胞比例增加，而同时是抑制STAT3和Notch信号通路时，与单独抑制Notch信号相比，不对称分裂比例下降，表明，抑制STAT3信号通路可通过减少不对称分裂模式而降低由抑制Notch信号通路再生毛细胞。
综上所述，STAT3信号通路参与内耳毛细胞发育过程。
STAT3，作为Notch信号下游分子，通过对称与不对称分裂方式调控内耳毛细胞的分化。
关键词：毛细胞，STAT3，Notch，Math1，对称不对称分裂Role of the STAT3 signaling pathway during Mammalianhair cell developmentAbstractHearing impairment incident is gradually increasing due to nosie, aminoglycosides and aging. Hearing loss, often caused by irreversible damage to hair cells or neuronal innervation defect, has been affecting millions of people in the world. Hair cells are mechanosensory cells that can directly convert sound into electrical signals. Therefore, understanding of mammalian hair cell differentiation mechanism and discovery of effective stimulators for hair cell generation are crucial for potential therapies of hearing loss.Hair cells, located adjacent to surrounding supporting in the organ of Corti, include one outer hair cell and three inner hair cells. Hair cell differentiation emerges at the mid-basal region of sensory epithelium at E14, and subsequently extends along the entire epithelium in basal-to-apical and medial-to-lateral fashions. Previous studies demonstrate that inner ear supporting cells, which retain stem cell features, have the capability to differentiate into hair cell in vitro. Over the past two decades, a number of genes and signaling pathways have been reported to regulate inner ear hair cell development. Of them, Notchsignaling has been shown to be a major player in the specification of prosensory epithelium and regulation of hair cell differentiation. Activation of Notch signaling contributes to choosing the sensory progenitor fate and maintaining their undifferentiated status. Inactivation of Notch signaling in conditional knockout mouse models or by pharmacological inhibitors induces an increase in hair cell production. Activation of Wnt signaling pathway enhance sensory epithelial cells proliferantion and differentiation. Another important factor is Math1, a bHLH transcription factor. Math1 is not only sufficient to induce differentiation of supporting cells into hair cells, but also required for hair cell differentiation. More recently, Jin et al. reported that in the zebrafish the signal transducer and activator of transcription 3 (STAT3) signaling, a classical pathway activated by extracellular factors, plays a role in regulation of zebrafish neuromast hair cell development. The zebrafish lateral line neuromasts are similar to the mammalian inner ear sensory epithelium in structure. STAT3 signaling is activated following hair cell damages and hair cell regeneration in the lateral line neuromasts. Knockdown of Stat3decreases the number of hair cells by downregulating Math1 expression during hair cell development. However, the importance of STAT3 signaling for mammalian inner ear hair cell differentiation and the relationship between STAT3 and Notch signaling pathways during this process are still unknown.On the other hand, normal tissue homeostasis is maintained through symmetric and asymmetric cell divisions of stem/progenitor cells. Symmetric divisions are required for the expansion of progenitor numbers, while asymmetric divisions are operated to give rise to differentiated cells. For instance, in developing prostates, basal cells display symmetric division to produce daughter cells with self-renewal capacity, and undergo asymmetric division to generate daughter cells to achieve both self-renewal and differentiation potential. Up to now, the cell division modes that the inner ear supporting cells undergo have never been examined and whether STAT3 signaling influences these cell division modes during hair cell differentiation has not been reported.In this study, using conditional STAT3 and Notch1 knockout mouse models and pharmacological inhibitors in otosphere-adhesive differentiation or cochlear explant cultures, the present study provides evidences for a role of STAT3 signaling in supporting cell proliferation and hair cell differentiation in mammalian cochleae.In the first Chapter, we found that STAT3 was diffused expressed in the cochlear prosensory epithelium at E14, and gradually restricted in the hair cells. Meanwhile, STAT3 pS727 was expressed in the hair cells. RT-qPCR assay showed that, adhesive otosphere cells displayed an increased mRNA level of Stat3, concomitant with up-regulated expression of Math1, as hair cell differentiation proceeded. STAT3 and itsactivated form STAT3 pS727 and STAT3 pY705 were expressed in the newly hair cells in the process of hair cell differentiation in vitro. To assess the role of STAT3 in regulating hair cell development, we introduced Sox2CreER;STAT3flox/flox mouse line in which Stat3can be deleted following induction of Cre activity. Sox2CreER;STAT3flox/flox mice displayed sensory epithelium disorganization, a reduction in hair cell numbers, and down-regulation expression of hair cell-related genes. Importantly, hair cell loss detected appear to more severe in the apical turn than that in the basal turn. Similarly, using explant culture and otosphere-adhesive differentiation culture, we found the reduction of hair cell number when STAT3 signaling pathway is blocked.Moreover, S3I-201 treatment increased BrdU+/Sox2+ and BrdU+/Prox1+ cell numbers, but decreased BrdU+/Math1-GFP+ cell number. By cell division mode analysis using double immunostaining for cell mitotic markers and supporting cell markers, or differentiated cell markers, we found that three cell division modes: symmetric self-renewal, symmetric commitment and asymmetric cell division. Inactivation of STAT3 signaling pathway induced a reduction in hair cell number, mediating by a shift from asymmetric division to symmetric division.In the second Chapter, we investigate the crosstalk between STAT3 and Notch signaling pathway in regulation of hair cell development. We found that STAT3 and STAT3 pS727 were expressed in ectopic hair cellsin the Sox2CreER;Notch1flox/flox mouse. STAT3 activated form (STAT3 pS727 and STAT3 pY705) were upregulated when Notch signaling pathway is inhibited, suggesting that perturbing Notch signaling may activate STAT3 siganling in the sensory epithelia. Inhibition of Notch signaling pathway led to the production of ectopic hair cells, an increase in hair cell number, a shift from symmetric division to asymmetrivc divisions of supporting cells. However, blocking STAT3 signaling attenuated the effects of the inhibition of Notch signaling, including a regression of disordered epithelium, a recovery from the reduction in the hair cell numbers, and a reversion of the cell division modes.In conclusion, STAT3 signaling is important for mammalian cochlear hair cell differentiation. It contributes to the down-stream of the Notch pathway in regulation of hair cell production via influencing the balance between symmetric and asymmetric division modes of supporting cells.Keywords：Hair cell，STAT3，Notch，Math1，Symmetric and Asymmetric cell division目录摘要 (I)Abstract ........................................................................................................................ I V 第一章绪论. (3)1.1 内耳的结构与发育 (3)1.2 STAT3 (16)1.3 对称及不对称分裂 (17)1.4 本论文课题的提出 (20)1.5 本课题研究内容和创新性 (21)第二章STAT3信号通路在哺乳动物内耳发育中的机制研究 (22)2.1 引言 (22)2.2 材料与方法 (23)2.2.1 仪器与设备 (23)2.2.2 实验动物 (25)2.2.3 实验材料 (25)2.2.4 条件性敲除小鼠基因型鉴定及Cre诱导 (28)2.2.5 内耳解剖 (31)2.2.6 RT-qPCR (32)2.2.7 免疫组化 (35)2.2.8 H&E染色 (36)2.2.9 耳蜗组织培养 (36)2.2.10 内耳支持细胞培养 (37)2.2.11 细胞和组织免疫荧光 (38)2.2.12 细胞培养 (39)2.2.13 质粒提取 (39)2.2.14 荧光素酶报告基因检测 (41)2.2.15 蛋白印迹法（Western blot） (41)2.2.16 统计学处理并分析 (44)2.3实验结果 (44)2.3.1分选Math1-GFP-的支持细胞 (44)2.3.2内耳毛细胞表达STAT3 (45)2.3.3STAT3在内耳组织的表达方式 (46)2.3.4毛细胞体外诱导分化体系的建立 (49)2.3.5STAT3在体外诱导毛细胞分化过程中的表达和定位 (49)2.3.6敲除STAT3抑制毛细胞发育 (51)2.3.7敲除STAT3降低毛细胞相关基因的表达 (52)2.3.8敲除STAT3抑制内耳毛细胞与神经元连接 (55)2.3.9STAT3敲除的小鼠在组织培养水平抑制早期毛细胞的发育 (56)2.3.10STAT3的敲除对后期毛细胞发育无明显作用 (57)2.3.11抑制STAT3在体外诱导体系中减少毛细胞的分化 (58)2.3.12STAT3信号通路正向调控Math1的转录活性 (61)2.3.13抑制STAT3信号通路降低由支持细胞分裂产生的毛细胞数目 (61)2.3.14STAT3失活降低早中期支持细胞分裂分化成毛细胞的进程 (63)2.3.15抑制STAT3信号通路促进支持细胞自我更新 (65)2.3.16内耳支持细胞通过对称不对称分裂模式产生毛细胞 (66)2.3.17失活STAT3信号通路抑制不对称分裂 (70)2.4讨论 (71)2.5本章小结 (74)第三章Notch与STAT3信号通路在毛细胞发育机制研究的关系 (75)3.1引言 (75)3.2材料与方法 (76)3.2.1仪器与设备 (76)3.2.2实验动物 (78)3.2.3实验材料 (78)3.2.4条件性敲除小鼠基因型鉴定及Cre诱导 (80)3.2.5内耳解剖 (83)3.2.6RT-qPCR (83)3.2.7免疫组化 (85)3.2.8耳蜗组织培养 (86)3.2.9分选支持细胞 (86)3.2.10内耳支持细胞培养 (87)3.2.11细胞和组织免疫荧光 (88)3.2.12蛋白印迹法（Western blot） (88)3.2.13统计学处理并分析 (91)3.3结果 (91)3.3.1敲除STAT3促进内耳Notch靶基因上调 (91)3.3.2体内敲除Notch1诱导STAT3的表达和活化 (92)3.3.3DAPT诱导内耳上皮STAT3活化 (93)3.3.4S3I-201抑制了DAPT诱导的毛细胞分化 (94)3.3.5S3I-201降低了由DAPT诱导的不对称分裂的比例 (95)3.3.6S3I-201提高了由DAPT诱导的Notch靶基因的下调 (98)3.3.7S3I-201降低了由DAPT诱导的毛细胞再生 (98)3.4讨论 (100)3.5本章小结 (101)全文总结 (102)研究展望 (104)中英文缩略词对照表 (106)参考文献 (107)致谢 (119)第一章绪论根据世界卫生组织（WHO）统计结果，全球有3.6亿人（占人口5%）有耳聋至残疾的听力损伤，约3200万为儿童；并且，60岁之上的人口有1/3，80岁之上的人口有9/10有耳聋的现象。
Notch信号通路简介命名由来：功能下调会导致果蝇翅膀缺刻。
【1】主要功能参与发育过程中的细胞分化。
参与决定细胞命运。
1.影响果蝇与脊椎动物的神经分化。
在果蝇Notum中，Notch首先确定有分化成神经潜能的细胞的数量（lateral inhibition），再决定这些细胞的后代中哪些分化成神经，哪些分化成神经胶质（lineage decisions）。
2.果蝇翅膀中Notch信号通路决定D-V界限，它的缺失可能引起翅的缺刻。
2龄幼虫开始形成背腹间隔，选择基因Ap(apterous)在翅膀的背区表达，诱导Fringe 和Serrate 在背隔间区表达，而Delta则在背腹区均有表达。
在背间隔区，Fringe抑制serrate 的功能，而促进Dl的功能。
所以，serrate在靠近DV界限的腹间隔区激活Notch(没有fringe),而Dl在靠近DV界限的背间隔区激活Notch(fringe激活其活性)。
Notch信号可能与癌症相关。
50% 的T-cell acute lymphoblastic leukaemias中都可以检测到Notch 1的突变。
Notch还参与调控血管的生成。
Notch信号可能与免疫相关。
它可以促进Tαβ细胞的形成，与Gata 3基因协同调控CD4+细胞向Th 1/Th 2 类型的分化[7]，并且可增加外周免疫器官边缘区B 细胞的数量。
¤- Notch信号通路只能影响相邻的细胞。
没有二级信使，信号传递速度快。
¤-相邻细胞可以通过Notch受体与配体的结合传递Notch信号，从而扩大并固化细胞间的分子差异，最终决定细胞命运，影响器官形成和形态发生。
¤-Notch信号在细胞中常被反复激活，决定不同的细胞命运。
（比如神经细胞的分化、比如翅形态建成）【2】信号通路的成员Serrate (Jagged1、Jagged2 in mammals) ★功能：Notch配体，激活受体细胞Notch信号通路。
细胞信号通路在肿瘤发生发展中的作用中文摘要：细胞信号通路在生物体中发挥着重要的作用。
肿瘤的发生和发展与细胞信号通路的异常有着紧密关联。
细胞信号通路可分为多个分支，其中包括WNT、NOTCH、JAK-STAT、PI3K-Akt和RAS-MAPK等分支。
这些信号通路在肿瘤发生和发展中起着不同的作用，可调控细胞的增殖、分化、凋亡和代谢。
此外，一些调节蛋白、激酶和转录因子也参与了肿瘤的发生和发展。
因此，细胞信号通路可能成为肿瘤治疗的重要靶点。
关键词：细胞信号通路；肿瘤；分支；增殖；凋亡英文摘要：Cell signaling pathways play an important role in the organism.The occurrence and development of tumors are closely related tothe abnormality of cell signaling pathways. Cell signaling pathways can be divided into many branches, including WNT, NOTCH, JAK-STAT, PI3K-Akt, and RAS-MAPK. These signaling pathways play different roles in the occurrence and development of tumors, and can regulate the proliferation, differentiation, apoptosis, and metabolism of cells. In addition, some regulatory proteins, kinases, and transcription factors are also involved in the occurrence and development of tumors. Therefore, cell signaling pathways may become an important target for tumor therapy.Keywords: cell signaling pathways; tumor; branch; proliferation; apoptosis小标题：一、细胞信号通路二、肿瘤的异常分子通路三、肿瘤的治疗靶点——细胞信号通路正文：一、细胞信号通路细胞信号通路是一种涉及细胞内和细胞间的信息传递系统。
