就结合我平时写intro的习惯和我看到什么样的intro会被吸引读下去，来记下点东西吧~

有点不太切题，请见谅。

借用生物学家 Itai Yanai 的一张图

右边的hourglass就是写作的过程了。 introduction大致对应 ’background on the field‘ 这一部分。

个人认为，取决于文章的目的，是填补了研究领域空白，还是更新了人们对某个现象的认知，或者精进了某种工具，做出了重大预测，不同的文章目的，对应不同的introduction写法。而文章写作，中外都一样，逻辑通顺是基本项，另外”文似看山不喜平“，introduction就是要调足读者胃口，formulate 好问题，点出关键gap或者之前研究的drawback，再给出自己的solution。

1, Problem formulation

虽然不同文章的第一段写法各有不同，个人比较喜欢 ’从第一性原理’ 出发的写法。第一段前两句，基本是’大白话‘，就是是个人就能看懂的话，这些话一般代表了所研究领域的first principle, 比如:

”Aging is a gradual process of functional and homeostatic decline in living systems. This decline results in increased mortality risk and disease prevalence, eventually resulting in death.“^[1]

"Organisms commonly experience a decline in their physiological functioning with age [1]. This phenomenon, referred to as ageing or senescence, has a negative impact on the overall performance of organisms, reduces their ability to access and metabolize resources and results in elevated mortality and/or reduced reproductive rate [2–4]."^[2]

这种类似’公理‘性质的描述，’不会错‘，同时指定了文章所处的研究领域。first principle两句话概括了，后面一般会有一个关键的 however。

2, 填补空白或制造冲突

这个however，就是要向别人demonstrate：我为什么要花费时间来读你的manuscript。根据study的具体内容，However后面可以接的句子大致分为两种：

2.1 这里有个gap！

”Aging phenotypes have been observed and hypotheses have been proposed for more than a hundred years (Weismann et al. 1891; Kirkwood 1977; Gladyshev 2013; López-Otín et al. 2013), but we do not yet know the cellular and molecular players that cause aging or how they differ between biological contexts.“^[3]

2.2 前人错了！

Without critical analysis, this correlation has been widely interpreted as a causal relationship. That is, functional importance of a node is thought to arise from its structural importance in the network [6,7,9,10]. If true, this interpretation suggests a biological significance of network structures and hence is fundamental to systems biology. We here challenge this view by proposing an alternative explanation of the centrality-lethality rule that does not invoke the network architecture. We then evaluate the new explanation with empirical data and demonstrate that the prevailing interpretation of the centrality-lethality rule is unlikely to be correct.^[4]

2.3 以前的研究展示了mixed evidence或者得出了conflict的结论，亟待reconcile！

However, the extent of this phenomenon, both across genes and tissues, remains unclear (5). Age-associated increases in the heterogeneity of gene expression have also been observed at the level of individual cell- to-cell variation; however, only some cell types appear to be impacted (6). In a recent study of immune T-cells from young and aged individuals, no difference in cell-to-cell variability was observed in unstimulated cells, however, upon immune activation the older cells appeared more heterogeneous (7). It is not known why some cell-types and not others may be more likely to exhibit increased cellular variability.^[5]

2.4 前人研究的技术手段受到限制

Due to methodological limitations, seminal studies on SGE (both at the mRNA and protein levels) have focused on only a handful of genes (Elowitz et al. 2002; Ozbudak et al. 2002; Chubb et al. 2006). ^[6]

However, direct detection of the proposed gene activation and inactivation events was not possible because new proteins from individual activation events were masked by proteins remaining from previous events as a result of the long half- lives of the fluorescent proteins used as the reporter.^[7]

Whether these results for TDH3 generalize to other genes is, however, unclear. Importantly, we still lack quantitative experimental data and understanding of the fitness effects of expression noise and its relationship to the optimality of mean protein abundances (Fig. 1b). Therefore, how these two expression phenotypes might co-evolve, especially given their mechanistic couplings by the transcriptional process, is still an open question (Fig. 1c).^[8]

3，my solution

在set up好research problem之后，’亟需一个答案‘或者’急需一个解决方法’就呼之欲出了。常见的句式比如 ”To address this, xxx", ‘Given these limitations, the most direct way to xxxx is to directly .... ", " To better understand influences on xxx in xxx, we have focused on xxxx", etc.

4，精彩乐透

introdunction的最后一段，可以简要概述自己的study做了什么，结果是什么，implication是什么（简单提一句，大头放在discussion里面写）。这样写的好处是，对于时间有限的读者，看到intro的最后一段就可以对全文有一个大致的预判和心理期望，在大致了解研究结果和意义的情况下，决定是否花费时间继续深读下去。

常见layout有：

In the present study, we hypothesized that xxx. We tested this hypothesis by xxx to discover xxx. We hypothesized that a model in which xxx. Our calculation suggests that xxx is under this constraint, but xxx. Our model further indicates that xxx, highlighting the important role of xxx. Both the xxx are subject to xxx. Finally, our computational xxx based on xxx can fully reproduce xxx patterns observed. Our results provide insights on unified design principles underlying xxx.^[9]

这四点共同构成了introduction的arch，类似小说中的人物高光，人设好不好，立不立得住，看的是introduction里面的起承转合。

5，偏离常规

research文章总是有章可循的~ 时不时突破常规的写法，会让人眼前一亮，比如从一个神话传说入手，从一个童话故事展开，借用一个’名人名言‘。比如：

Eos, the Greek goddess of Dawn, asked Zeus to grant immortality to her mortal husband, Tithonus. Zeus honored her request, but as Tithonus grew older, he shriveled, becoming deaf, disabled and helpless because Eos asked for eternal life but not eternal youth. Inspired by this Greek myth, George C. Williams (1999) argued that biogerontology, too, has committed the Tithonus error. We have focused too much on life span and interventions that can extend life span. But healthy aging is just as much about the quality of our life and death as it is about the quantity of life. In fact, this concern has been with us for some time – Williams’ essay revisits themes that had been explored some three decades earlier by Leonard Hayflick (1971). Still, we know very little about the genetic relationships between age-related changes in demographic traits and functional traits that ultimately shape demographic traits (Grotewiel et al., 2005).^[10]

The importance of knowinga priorithe tractability of a question to be addressed is widely recognized in mathematics, physics, and chemistry (Ayoub, 1982;Feldman and Crutchfield, 1998;Allu and Oprea, 2005;Lopezruiz et al., 2010). For example, the competition for finding a general formula for solving equations of degree five had lasted ∼300 years since the successes in equations of degree three and degree four in the 16th century, and ended in the 19th century when the impossibility of such a general formula was proved; the subsequently developed group theory that gives an effective criterion for the solvability of all polynomial equations formed the basis of modern algebra (Ayoub, 1982;Rosen, 2016). However, biology as a branch of science dominated by empirical solutions has seldom been guided by such wisdoms.^[11]

参考

1. ^Kimmel, Jacob C., et al. "Murine single-cell RNA-seq reveals cell-identity-and tissue-specific trajectories of aging." Genome research 29.12 (2019): 2088-2103.
2. ^Malacrinò, Antonino, et al. "Ageing desexualizes the Drosophila brain transcriptome." Proceedings of the Royal Society B 289.1980 (2022): 20221115.
3. ^Kimmel, Jacob C., et al. "Murine single-cell RNA-seq reveals cell-identity-and tissue-specific trajectories of aging." Genome research 29.12 (2019): 2088-2103.
4. ^He, Xionglei, and Jianzhi Zhang. "Why do hubs tend to be essential in protein networks?." PLoS genetics 2.6 (2006): e88.
5. ^Yamamoto, Ryo, et al. "Tissue-specific impacts of aging and genetics on gene expression patterns in humans." bioRxiv (2021).
6. ^Barroso, Gustavo Valadares, Natasa Puzovic, and Julien Y. Dutheil. "The evolution of gene-specific transcriptional noise is driven by selection at the pathway level." Genetics 208.1 (2018): 173-189.
7. ^Raj, Arjun, et al. "Stochastic mRNA synthesis in mammalian cells." PLoS biology 4.10 (2006): e309.
8. ^Schmiedel, Jörn M., Lucas B. Carey, and Ben Lehner. "Empirical mean-noise fitness landscapes reveal the fitness impact of gene expression noise." Nature Communications 10.1 (2019): 1-12.
9. ^Cheng, Yang, et al. "Dominant constraints on the evolution of rhythmic gene expression." bioRxiv (2022).
10. ^Burger, Joep MS, and Daniel EL Promislow. "Are functional and demographic senescence genetically independent?." Experimental Gerontology 41.11 (2006): 1108-1116.
11. ^Liu, Li, et al. "The expression tractability of biological traits shaped by natural selection." Journal of genetics and genomics 46.8 (2019): 397-404.