給大家一個(gè)偽命題：文章和基金哪個(gè)更重要,？

如果真要分個(gè)你死我活，單選題的話(huà),，還真不好說(shuō)呢,，因?yàn)楸旧砦恼潞突鹗窍噍o相成的關(guān)系?？梢哉f(shuō)是：基金是雞蛋,，文章是母雞。

你說(shuō)雞蛋重要還是母雞重要,？哪個(gè)先哪個(gè)后,？真不好講。

所以我們提倡：兩個(gè)都很重要,，兩手都要抓,，哈哈。

今天我們來(lái)學(xué)習(xí)學(xué)習(xí)一個(gè)科研熱點(diǎn)：細(xì)胞程序性死亡,。

今天先說(shuō)其中有個(gè)細(xì)胞焦亡概念,，再說(shuō)必要性。先說(shuō)2018基金中細(xì)胞焦亡的項(xiàng)目。

首先咱們看看2018年醫(yī)學(xué)部細(xì)胞焦亡的情況：

2018年醫(yī)學(xué)部主題有“細(xì)胞焦亡”的項(xiàng)目共 79 條查詢(xún)結(jié)果,，累計(jì)金額：3081.0 萬(wàn)元

面上項(xiàng)目例子如下：

青年項(xiàng)目例子如下：

然后一起瀏覽下2019年里那些發(fā)表在神級(jí)期刊上的“細(xì)胞死亡”為主題的綜述文章,，大家如果有申請(qǐng)基金的朋友，一定要引用,。

1.The Coming Decade of Cell Death Research: Five Riddles.

Cell31.3981區(qū). 2019 May 16

英文摘要：Active cell death, in its many forms, is a fundamental biological process. Studies over the past several decades have explored the functions and consequences of cellular demise and elucidated several of the key cell death pathways. Here, I pose five questions, or riddles, that might provide a guide to the next decade of cell death research. Focusing mainly on four types of active cell death (apoptosis, necroptosis, pyroptosis, and ferroptosis) mainly in mammals, this Perspective explores the possible research directions that might answer these riddles, or at least prompt new ones.

本綜述將細(xì)胞死亡的幾種方式都進(jìn)行了詳細(xì)的概括,。在機(jī)體發(fā)育的過(guò)程中，一些細(xì)胞的死亡可以以一種“程序性”的方式來(lái)實(shí)現(xiàn)的,。在機(jī)體發(fā)育的過(guò)程中,，細(xì)胞死亡能夠被誘導(dǎo)或者預(yù)測(cè)，而且這些過(guò)程中涉及到許多物質(zhì)的參與,，這引起了研究人員們的興趣,，以探究細(xì)胞死亡背后的基因或者生物學(xué)過(guò)程。隨著分子生物學(xué)技術(shù)的進(jìn)步,，細(xì)胞死亡的研究進(jìn)入了高速發(fā)展時(shí)期,，在1990-2010這20年里，關(guān)于細(xì)胞死亡的調(diào)控研究文章獲得大量發(fā)表,。

本文中作者提出了細(xì)胞死亡的5個(gè)科學(xué)問(wèn)題,，有助于思索。

• 什么程度的死亡是細(xì)胞死亡,？

• 什么情況下對(duì)細(xì)胞有毒的物質(zhì)不再起作用,？

• 細(xì)胞死亡到底有多重要？

• 一個(gè)細(xì)胞的死亡會(huì)對(duì)周?chē)募?xì)胞產(chǎn)生影響嗎,？

• 細(xì)胞死亡到底有多少形式,？

我們都知道已知的細(xì)胞程序性死亡方式有：apoptosis, necroptosis, pyroptosis, and ferroptosis。它們分別是細(xì)胞凋亡,，細(xì)胞壞死,，細(xì)胞焦亡，以及鐵死亡,。

細(xì)胞焦亡

鐵死亡

2.Innate immunity to intracellular LPS.

Rathinam VAK, Zhao Y, Shao F.

Nat Immunol21.8091區(qū). 2019 May

摘要：Monitoring of the cytosolic compartment by the innate immune system for pathogen-encoded products or pathogen activities often enables the activation of a subset of caspases. In most cases, the cytosolic surveillance pathways are coupled to activation of caspase-1 via canonical inflammasome complexes. A related set of caspases, caspase-11 in rodents and caspase-4 and caspase-5 in humans, monitors the cytosol for bacterial lipopolysaccharide (LPS). Direct activation of caspase-11, caspase-4 and caspase-5 by intracellular LPS elicits the lytic cell death called 'pyroptosis', which occurs in multiple cell types. The pyroptosis is executed by the pore-forming protein GSDMD, which is activated by cleavage mediated by caspase-11, caspase-4 or caspase-5. In monocytes, formation of GSDMD pores can induce activation of the NLRP3 inflammasome for maturation of the cytokines IL-1β and IL-18. Caspase-11-mediated pyroptosis in response to cytosolic LPS is critical for antibacterial defense and septic shock. 

這次是國(guó)內(nèi)細(xì)胞焦亡牛人邵峰教授的文章,，發(fā)表在了Nature子刊上。

2019年4月8號(hào),，邵峰團(tuán)隊(duì)等人在Nature immunology上發(fā)表了Innate immunity to intracellular LPS的綜述性文章,。在這里，研究人員回顧了關(guān)于細(xì)胞溶質(zhì)LPS感知及其調(diào)節(jié)和病理生理功能的最新研究進(jìn)展,。

致病菌入侵宿主時(shí)產(chǎn)生的物質(zhì)可誘導(dǎo)一系列的caspases蛋白酶的激活,。Caspase全稱(chēng)為含半胱氨酸的天冬氨酸蛋白水解酶(cysteinyl aspartate specific proteinase)。caspase是一組存在于細(xì)胞質(zhì)中具有類(lèi)似結(jié)構(gòu)的蛋白酶,。Caspase與真核細(xì)胞凋亡密切相關(guān),，并參與細(xì)胞的生長(zhǎng),、分化與凋亡調(diào)節(jié)。

一般來(lái)說(shuō),，細(xì)胞監(jiān)控通路會(huì)通過(guò)炎癥小體復(fù)合物和Casp1的激活緊密相連,。在嚙齒類(lèi)動(dòng)物中的CASP-11以及人類(lèi)中CASP-4以及CASP-5，會(huì)被細(xì)菌產(chǎn)生的LPS激活,，而這些蛋白酶的激活會(huì)導(dǎo)致一種細(xì)胞程序性死亡形式：細(xì)胞焦亡,。而細(xì)胞焦亡具體執(zhí)行是通過(guò)一個(gè)蛋白叫做GSDMD，其可以在細(xì)胞膜結(jié)構(gòu)上形成聚合體,，進(jìn)行“打洞”,，導(dǎo)致細(xì)胞的滲透壓?jiǎn)适В鳪SDMD核孔的形成進(jìn)而導(dǎo)致NLRP3炎癥小體的激活,，進(jìn)行促進(jìn)了成熟體IL-1β以及IL-18的形成,。

3.Diverging inflammasome signals in tumorigenesis and potential targeting.

Nat Rev Cancer42.7841區(qū). 2019 April

摘要：Inflammasomes are molecular platforms that assemble upon sensing various intracellular stimuli. Inflammasome assembly leads to activation of caspase 1, thereby promoting the secretion of bioactive interleukin-1β (IL-1β) and IL-18 and inducing an inflammatory cell death called pyroptosis. Effectors of the inflammasome efficiently drive an immune response, primarily providing protection against microbial infections and mediating control over sterile insults. However, aberrant inflammasome signalling is associated with pathogenesis of inflammatory and metabolic diseases, neurodegeneration and malignancies. Chronic inflammation perpetuated by inflammasome activation plays a central role in all stages of tumorigenesis, including immunosuppression, proliferation, angiogenesis and metastasis. Conversely, inflammasome signalling also contributes to tumour suppression by maintaining intestinal barrier integrity, which portrays the diverse roles of inflammasomes in tumorigenesis. Studies have underscored the importance of environmental factors, such as diet and gut microbiota, in inflammasome signalling, which in turn influences tumorigenesis. In this Review, we deliver an overview of the interplay between inflammasomes and tumorigenesis and discuss their potential as therapeutic targets.

炎癥小體是基于細(xì)胞內(nèi)源的各種刺激信號(hào)而激活的分子平臺(tái)，其激活和組裝導(dǎo)致了Caspase-1的激活,，因此促進(jìn)了成熟體IL-1β以及IL-18的形成和分泌，造成了細(xì)胞焦亡,。炎癥小體的效應(yīng)分子們最初是為了抵抗細(xì)菌的感染而起到機(jī)體保護(hù)作用的,。然后異常的炎癥小體信號(hào)通常和很多代謝疾病、炎癥疾病,、神經(jīng)退行性疾病以及腫瘤的發(fā)生有關(guān),。由炎癥小體介導(dǎo)的慢性炎癥反應(yīng)在腫瘤的發(fā)生、免疫抑制,、增殖,、血管生成以及轉(zhuǎn)移過(guò)程中起著中心調(diào)控作用。相反的,，炎癥信號(hào)通路也可以通過(guò)介導(dǎo)小腸屏障完整性而起到抑制腫瘤抑制的作用,，扮演著相反的角色。眾多研究表明環(huán)境因素例如飲食,、腸道微生物在炎癥小體信號(hào)通路中也發(fā)揮著重要的作用,。

4.The molecular machinery of regulated cell death.

Cell Res15.3931區(qū). 2019 May

Cells may die from accidental cell death (ACD) or regulated cell death (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms of RCD have been identified and are increasingly being implicated in various human pathologies. Here, we critically review the current state of the art regarding non-apoptotic types of RCD, including necroptosis, pyroptosis, ferroptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis and oxeiptosis. The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.

各種各樣的細(xì)胞死亡方式

這篇文章作者從細(xì)胞可能發(fā)生的死亡方式講起，分為兩種一種是不可預(yù)知的死亡,，另外一種就是細(xì)胞程序性死亡,。有特定的分子機(jī)制模式，各個(gè)步驟之間有嚴(yán)格的調(diào)控機(jī)制,。這篇文章主要討論非凋亡的其他細(xì)胞程序性死亡包括：細(xì)胞壞死,、細(xì)胞焦亡、鐵死亡,、entotic cell death（小編也解釋不清）,、 netotic cell death（小編也解釋不清）,、parthanatos（見(jiàn)如下解釋?zhuān)⑷苊阁w依賴(lài)的細(xì)胞死亡,、自噬介導(dǎo)的細(xì)胞死亡,、一種依賴(lài)于堿性pH內(nèi)環(huán)境的細(xì)胞死亡新形式堿死亡（alkaliptosis）、氧化應(yīng)激介導(dǎo)的死亡等等,。

P.S 2007年,，約翰霍普金斯大學(xué)醫(yī)學(xué)院Ted Dawson與Valina Dawson夫妻發(fā)現(xiàn)了程序性腦細(xì)胞死亡的一種新形式，他們將其命名parthanatos(thanatos: 希臘神話(huà)中死亡的象征),，這種新的細(xì)胞死亡方法出現(xiàn)在中風(fēng),、阿爾茨海默癥、帕金森病和罕見(jiàn)的致命遺傳疾病亨廷頓病中