气体信号递质(gasotransmitters)又称气体信号分子,是一类细胞内源性小分子气体,参与细胞内诸多信号转导途径,在动植物代谢及其调控中发挥着不可替代的重要作用。经过二十多年的发展,科学家们已经逐步认识到除了一氧化氮(NO)、一氧化碳(CO)和硫化氢(H₂S)三种经典气体信号递质外,氢气(H₂)和甲烷(CH₄)等多种气体均可能是潜在的气体信号递质。
总体看,越来越多的研究成果展示出气体信号递质在医学和农业等领域所具有的理论意义和巨大应用潜力。气体递质的相关研究加深了我们对医学领域细胞信号转导过程的理解,同时也引起了植物领域研究者的广泛兴趣。本专栏以气体信号递质为主题,除了特邀长期从事相关研究领域的专家总结研究进展外,还收集了5篇气体信号递质方面的研究论文,以期为相关领域的研究者提供参考。
南京农业大学生命科学学院谢彦杰教授等在“硫化氢调节植物氧化应激响应的作用机制”一文中总结了植物中H₂S产生途径,以及H₂S、活性氧(reactive oxygen species, ROS)和活性氮(reactive nitrogen species, RNS)在调节植物氧化应激响应中的研究进展;山西大学生命科学学院的裴雁曦教授等在“硫化氢信号对大白菜FLCs时空表达模式的调控作用”研究论文中发现H₂S可能是通过调节大白菜中4个BrFLCs同源基因的表达影响植物开花;针对H₂S在植物能量代谢中扮演的角色,山西大学生命科学学院金竹萍教授等在“H₂S信号参与SDH调控能量和活性氧代谢过程的作用机制”研究论文中,初步揭示了H₂S信号与电子传递链之间的关系,并探索H₂S在能量代谢和ROS平衡过程中的相关调节机制;针对H₂S是否通过氧化应激调节动物衰老过程这一问题,厦门大学医学院李鸿珠教授在“硫化氢抗衰老作用的分子机制”一文中,从抑制氧化应激、抗炎、保护线粒体功能、维持蛋白质稳态和上调自噬方面总结了H₂S抗衰老的分子机制,讨论了目前研究存在的问题和未来研究方向,尝试为抗衰老和治疗衰老相关疾病提供新的思路。
与H₂S相类似,NO在农产品保鲜中也具有抗衰老作用。甘肃农业大学廖伟彪教授等在“一氧化氮在延缓农产品采后衰老中的作用机制”中针对NO延缓农产品采后衰老的作用机制,系统地总结了NO与褪黑素、乙烯(ETH)、H₂、H₂S、过氧化氢和钙离子等信号分子的互作,从而为利用NO以及衍生物延缓农产品衰老、提高储藏品质的理论研究,以及农产品采后保鲜剂的研发提供参考;华中农业大学植物科学技术学院吴洪洪教授团队在“CeO₂纳米颗粒调控活性氧稳态和一氧化氮水平提高水稻耐旱能力”研究论文中,从ROS和NO信号分子的角度,初步探索了氧化铈纳米颗粒提高水稻抗旱性的机制,从而丰富了纳米农业可持续发展的理论。
作物对重金属耐受和富集问题一直是现代农业生产实践中的重要命题。西北农林科技大学生命科学学院李积胜教授团队在“乙烯促进木质素合成减少镉吸收和积累提高番茄耐镉性”的论文中发现Cd²⁺胁迫提高了番茄幼苗ETH合成关键蛋白甲硫氨酸腺苷转移酶(methionine adenosyltransferase,MAT)活性,并提出MAT介导的ETH合成可能是番茄提高耐镉性的分子机制,从而为ETH在果蔬作物安全生产实践提供了初步的理论依据。
H₂是近来发现的一种潜在的气体信号递质。针对上述热点问题,河南师范大学生命科学学院段红英教授等在“氢气处理促进地黄生长发育及主要药用成分积累”一文中的研究结果表明纳米富氢水处理不仅可以促进地黄生长发育,还可以通过调控环烯醚萜苷合成通路关键酶基因,提高地黄药用成分积累,为H₂在中药材生产中的应用提供了新思路。
云南师范大学生命科学学院李忠光教授撰写的“气体递质:古老气体在植物响应温度胁迫中的新角色”一文,系统地总结了包括H₂S、NO、CO、ETH、H₂、CH₄等9种具备气体信号递质基本特征的分子在植物代谢和胁迫应答中的作用和最新研究进展,详细介绍了信号分子的特性、合成代谢、分解代谢及其相互作用,并从抗氧化系统、渗透调节系统、离子平衡系统、水平衡系统、热激蛋白、翻译后修饰和生物膜修复与重建的角度,综述了气体信号递质生物学作用的生物化学和分子生物学基础。
与已知的气体信号递质不同,氩气作为一种具有潜在生物学功能的气体,逐渐引起了科学家的注意。南京农业大学生命科学学院沈文飚教授团队在“方兴未艾的氩气生物学”一文中总结了氩气生物学效应及其潜在的分子机制,包括氩气的不同施用方式以及在动物神经保护、心血管疾病、炎症性疾病和器官移植等临床模型中的正面作用,并总结了其在农产品采后保鲜和植物耐逆性方面的研究进展,提出酶蛋白的磷酸化与脱磷酸化修饰可能是其生物学效应的重要分子机制。
总体看,气体信号递质调控的生理和病理代谢是一个极其复杂的调控过程,其相关研究已经逐步从动物扩大到植物,体现其生物学作用的广泛性。希望通过本专栏的文章,让读者进一步认识气体信号递质的功能及其在农业实践和临床诊疗中的潜在应用,吸引更多的研究者投入到相关领域的研究中,以期全面、深入地解析气体信号递质的生物学功能和作用机理。

Argon is the most abundant inert gas in the atmosphere. For the past few years, the biological functions of argon have been discovered and gradually recognized by scientists. Argon, as a gaseous molecule with cytoprotective functions, could positively affect the physiological and pathological processes to varying degrees. Compared with the classic gasotransmitters, argon is non-toxic, harmless, and abundant, attracting extensive attention in all professions. This review outlined the biological effects and the potential molecular mechanisms of argon, and summarized the supply methods and the positive roles of argon in neuroprotection, cardiovascular disease, inflammatory disease, organ transplantation, and other animal clinical models, and also overviewed the research progress in post-harvest preservation of agricultural products and plant tolerance to abiotic stress. The mechanisms in the above studies about the biological effects of argon were closely related to argon control of receptors, ion channel proteins, reprogramming gene expression, and re-establishment of redox and ion homeostasis. Meanwhile, argon-regulated phosphorylation and dephosphorylation modification in enzyme proteins might be crucial in argon biology. The potential applications of argon have excellent prospects in medicine and agriculture with security and cost advantages.

Oxidative stress is a state of redox imbalance, and it easily leads to oxidative damage in an organism. The main mechanism of oxidative stress is to regulate the redox balance by activating the antioxidant system. As an important signaling molecule, hydrogen sulfide(H₂S) participates multiple physiological reactions and stress response in living beings. Here, we review the production pathway of H₂S in plants and the characteristics of common H₂S donors. Furthermore, we also introduce the progress of H₂S, reactive oxygen species(ROS) and reactive nitrogen species(RNS) in regulating the oxidative stress in plants. We particularly emphasized the regulatory mechanisms of H₂S in the stress response and its mutual adjustment with ROS and RNS in redox homeostasis in plants. This review provides a reference for understanding the signaling mechanism in the oxidative stress response in plants.

Gas molecules including hydrogen sulfide, nitric oxide, carbon monoxide, ethylene, hydrogen gas, ammonia, methane, hydrogen cyanide, and sulfur dioxide were the main components of primitive atmosphere on the earth four billion years ago. Nowadays, these gases are viewed as gasotransmitters(GTs) in organisms, namely endogenously gaseous molecules. GTs not only regulate many physiological and pathological processes, such as breathing, blood pressure, learning, memory, and the inflammatory response in animals, but also play a key role in the stomatal movement,seed germination, plant growth, development, and response to environmental stress. In thisreview, we cover the current progress on the metabolism of GTs, their response to temperature stress in plants, and their general characteristics, anabolism, catabolism. In addition, we highlight the key role of the antioxidant system, the osmoregulation system, the ion balance system, the water balance system, heat shock proteins, post-translational modifications, and re-establishment and repair of biomembranes in the mitigation of oxidative stress, osmotic stress, ion stress, water stress, protein denaturation, and biomembrane injury induced by temperature stress. The alleviation of these injuries could increase the resistance of plants to high temperature and low temperature stresses. Furthermore, we summarize the interactions among GTs by initiating chemical reaction, regulating metabolic enzymes, competing target molecules, and triggering new signaling to modulate temperature stress tolerance in plants. The aim of this review is to drive the rapid progress on GTs in the field of plant biology in the future.

Nitric oxide(NO) is essential for reducing post-harvest product senescence and storage losses. NO may slow down the senescence of agricultural products and improve their quality, suggestive of its great potential in the postharvest preservation of agricultural products. The development of NO as a post-harvest preservative is supported by the investigation of its role and mechanism in agricultural product ageing. In this review, the mechanisms of NO in the post-harvest senescence of agricultural products were explored. NO is produced mainly via the nitrate reductase(NR) and NO synthase-like(NOS) pathways. Usually, NO donors include sodium nitroprusside(SNP), S-nitroso-N-acetyl-DL-penicillamine(SNAP), S-nitrosoglutathione(GSNO) and NO gas fumigation. NO delays agricultural product senescence by regulating ROS metabolism, enhancing antioxidant activity, reducing respiration, activating cell wall metabolism, inhibiting ethylene synthesis, and promoting energy metabolism. Melatonin(MT), ethylene(ETH), hydrogen gas(H₂), hydrogen sulfide(H₂S), hydrogen peroxide(H₂O₂) and calcium ion(Ca²⁺) may interact with NO to further regulate agricultural product ageing. This review may provide a reference for the use of NO to delay senescence, improve storage quality, and develop post-harvest preservatives for agricultural products.

Aging contributes to age-related diseases such as cardiovascular diseases, diabetes, and Alzheimer’s disease, which are characterized by imbalance of protein homeostasis, accumulation of oxidative damage, stem cell failure, altered intercellular communication, chronic inflammation, and microecological disorders. It is well known that hydrogen sulfide(H₂S) is an endogenous gas signaling molecule that widely exists in all kinds of organisms from bacteria to plants and animals. In the human body, H₂S can regulate cell signal transduction through S-sulfhydration modification of proteins at physiological concentrations. Recent studies have found that aging is accompanied by a decrease in the production of endogenous H₂S and a general decline of protein S-sulfhydration. Exogenous H₂S can inhibit body aging. In some age-related diseases such as Alzheimer’s disease, senile myasthenia gravis and osteoporosis, anappropriate amount of exogenous H₂S plays anti-aging effect. This review summarizes the molecular mechanisms of H₂S in antagonizing aging, including inhibition of oxidative stress, inhibition of inflammation, protection of mitochondrial function, maintenance of protein homeostasis and up-regulation of autophagy. We also discuss the issues and frontiers in the anti-aging mechanism of H₂S, so as to provide new ideas for inhibiting aging and the treatment of aging-related diseases.

Hydrogen sulfide(H₂S) has been recognized as a new gasotransmitter with diverse functions in plants under physiological, pathogenic and adverse environmental conditions. Succinate dehydrogenase(SDH), bound to the inner mitochondrial membrane, is the only enzyme shared by both the electron transport chain and the tricarboxylic acid cycle in mitochondria, playing an important role in plant responses to various stresses. In view of the correlation between H₂S and SDH involved in diverse physiological processes, their relationship between the two with Arabidopsis was exploredin this paper. The results showed that LCD and DES1, two genes encoding H₂S production enzymes in Arabidopsis, were abundantly expressed in AtSDH1-1-OE, and the H₂S production was significantly higher compared to WT. TTFA(SDH inhibitor) induced massive ROS production and significantly inhibited seedling root elongation, as well as down-regulated the expression of root growth related genes RHD2, TRH, and SCN1. However, physiological concentrations of NaHS(H₂S donor) cleared the excess ROS induced by TTFA, and seedling growth was restored to some extent. The application of HT(H₂S scavenger) impaired root growth in AtSDH1-1-OE, which was similar to the treatment of TTFA in WT. H₂S- specific fluorescence probe and NMT assays also indicated that TTFA and HT induced an increase of H₂O₂ in guard cells, while H₂S could drive its efflux. In addition, H₂S affected the expression of genes related to ATP synthesis and contributed to the production of ATP. Accordingly, the ATP content was significantly reduced by applying HT in AtSDH1-1-OE. In summary, SDH could induce the production of endogenous H₂S in plants, which in turn is involved in the regulation of energy metabolism and ROS production in plants by SDH and eventually affects the elongation of the roots.

Hydrogen gas(H₂) plays the diverse and positive roles for improving crop yield and quality. Due to the influences of cultivated methods, chemical fertilizers and pesticides, the yield and quality of R.glutinosa have been seriously restricted. Herein, “Jinjiu”R. glutinosa was used as the material to explore the effects of hydrogen nanobubble water(HNW) on the growth, development and the accumulation of the main medicinal components at different stages. Compared with controls, the number of adventitious roots and the germination rate were increased by about 217.59% and 87.65%, respectively, after 7 days(d) of HNW treatment.Compared to controls, after HNW treatment for 60, 75 and 90 d, the leaf crown breadth had increased by approximately 42.73%, 53.02% and 29.42%, respectively. And the maximum leaf area was elevated by approximately 15.51%, 19.74% and 11.44%. After 75 and 90 d with HNW supplement, the number of enlarged roots was increased by about 105.65% and 66.82% than controls, respectively. The analysis of gene expression of iridoid glycoside synthesis pathway enzyme(1-deoxyxylulose-5-phosphate synthetase, DXS; geraniol 10-hydroxylase, G10H; 1-deoxy-D-xylulose-5-phosphate reductase, DXR; 8-hydroxygeraniol dehydrogenase, 10HGO) by using real-time quantitative PCR confirmed that the transcript levels of RgDXS2, RgG10H1 and RgDXR1 were significantly upregulated(about 2.61-, 1.27- and 3.32-fold), after being treated with HNW for 75 d. After 90 d of HNW treatment, the expression levels of RgDXS2, RgG10H1 and Rg10HGO1 were approximately 4.11-, 1.24- and 1.77-fold higher than controls. The analysis for medicinal components by high-performance liquid chromatography showed that, compared to controls, after 75 and 90 d of HNW treatment, the catalpol content was increased by roughly 103.96% and24.94%, respectively. And the rehmannin D content was elevated by 33.14% after 75 d of HNW treatment. In addition, treatment with HNW significantly increased the number of enlarged roots at 120 d, while the transcript levels of RgDXR1, RgG10H1 and Rg10HGO1 were increased by approximately 2.00-, 1.32- and 1.36-fold, respectively.In summary, HNW not only promoted the growth and development of R. glutinosa, but improved the accumulation of the main medicinal components by regulating the gene expression of iridoid glycoside synthesis pathway enzymes.

Hydrogen sulfide(H₂S), a signaling gasotransmitter, can promote flowering, a process that could be related to FLOWERING LOCUS C(FLC) in our previous experiments.Four FLC homologs have been reported in Brassica rapa. In the current study, we explored the spatiotemporal expression patterns of BrFLC homologs under H₂S treatment in Chinese cabbage to not only determine the differentiation of FLC homologs, but also analyze the effect of H₂S on their expression.The expression patterns of BrFLC1, 2 and 3 were consistent with that of AtFLC, whereas there were no significant changes in the expression of BrFLC5. BrFLC1 was expressed almost exclusively in leaves and cotyledons, whereas BrFLC2 was detected in various development stages. There was no noticeable change in BrFLC3 and 5 in the tissues examined, although BrFLC3 always showed the highest expression. Overall, BrFLC expression was slightly downregulated following exogenous H₂S treatment, with a minimum accumulation of BrFLC2 in leaves. Thus, H₂S appears to be able to regulate the downstream genes of BrFLCs to varying degrees and the variation in the expression patterns of downstream genes could be the result of the level of S-sulfhydration of H₂S and the functional diversity of the BrFLCs.So H₂S could have a place in regulating the expression of BrFLCs.

Cadmium(Cd) stress seriously inhibits the growth and development of plants, and Cd is enriched in the human body along the food chain, causing major risks to human health. Ethylene(ETH) is known for its role as a traditional plant hormone that plays a crucial part in various stress responses. However, the precise mechanisms by which ETH regulates plant tolerance to Cd remain unclear. In this study, we observed that treatment with 3 mg L^-1 Cd²⁺ significantly increased the activity of Methionine adenosyltransferase(MAT) and the content of S-adenosylmethionine(SAM), resulting in about a 44.6% rise in ETH content in roots. Further investigations revealed that ETH concentrations of 10 and 50 μmol/L enhanced the activity of enzymes involved in lignin synthesis, including phenylalanine ammonia-lyase(PAL), 4-coumarate coenzyme A ligase(4CL), cinnamyl alcohol dehydrogenase(CAD), and Guaiacolperoxidase(PPOD), thereby leading to about 52.1% and 83.8% increase in lignin synthesis, respectively, resulting in increased lignification of cell walls. Compared to the control group, ETH effectively hindered the influx of Cd²⁺in root epidermal cells by 40.2%-52.7% and reduced intracellular Cd accumulation in roots(P＜0.05). Furthermore, ETH reduced the content of water-extractable and ethanol-extractable Cd, which are highly toxic. Conversely, it increased the content of hydrochloric acid-extractable, acetic acid-extractable, sodium chloride-extractable, and residual Cd, which have a lower toxicity. Moreover, ETH also increased proportion of Cd in the cell wall while reducing its presence in organelles. Consequently, ETH led to a reduction in electrolyte leakage(EL) and malondialdehyde(MDA) contents, increased the levels of chlorophyll, and improved the plants’ tolerance toCd²⁺ stress. In conclusion, our findings found the changes of MAT enzyme activity under Cd²⁺ stress.We propose that there may be a correlation between MAT-mediated ETH synthesis and Cd²⁺ stress, which provided a new possible mechanism for ETH to alleviate Cd damage in plants. Our work also provides a primary theoretical foundation into the potential application of ETH in the safe production of vegetable crops.

Drought is a common limiting factor affecting rice yield and quality. Cerium oxide nanoparticles(nanoceria) have been widely reported to improve crop stress tolerance. However, the effects and mechanisms of nanoceria on rice drought tolerance are still unknown. The aim of this study is to investigate whether nanoceria can improve rice drought tolerance by modulating reactive oxygen species(ROS) homeostasis and nitric oxide(NO) levels. Our results showed that compared with no-nanoparticle treatment, nanoceria significantly increased the fresh weight of rice seedlings under drought stress(19%, P < 0.05). Also, under drought stress, the ROS level of rice leaves treated with nanoceria was significantly lower(82%, P < 0.05) than leaves treated with buffer. The leaf NO level after nanoceria treatment, however, is significantly higher(46%, P < 0.05) than that with no-nanoparticle treatment under drought stress. Moreover, compared with control plants, nanoceria maintained better membrane integrity in rice leaf cells under drought stress, showing a 70% decrease(P < 0.05) in dead leaf cells. This study explores the mechanisms underlying nanoceria’s improved rice drought tolerance by affecting ROS and NO levels, which not only further enriches our knowledge about the interaction between nanoparticles and crops under abiotic stress but also gives more support on the sustainable development of nano-enabled agriculture.

山东第一医科大学动脉粥样硬化研究所和第二附属医院的秦树存受邀撰写的“新的脂代谢调控基因-货运受体Surf4”一文，系统介绍了Surf4蛋白作为货运受体如何参与载脂蛋白在内质网与高尔基体之间的转运，进而影响肝细胞极低密度脂蛋白和小肠上皮细胞乳糜微粒分泌。希望深化人们对Surf4的认知，为其潜在的应用转化提供新的思路。血浆脂蛋白的组成和水平反映了机体内脂质代谢状态，临床检测已经把血浆脂蛋白检测作为常规指标，如何利用脂蛋白水平评价代谢性疾病患病风险、发展状况和治疗效果是临床医生普遍关心的问题。深圳大学化学与环境工程学院食品营养与安全实验室的何庆华围绕这些问题进行了“脂蛋白及其亚类在机体中的功能”的综述和展望。脂肪组织是体内脂代谢的重要场所，近年来对脂肪组织中巨噬细胞在脂代谢过程中的作用有了新的认识。西北农林科技大学的庞卫军在“脂肪组织中巨噬细胞在肥胖过程中的作用及其调控机制”一文中总结出巨噬细胞参与肥胖调控的4条主要途径，值得读者仔细阅读和学习。此外，质膜磷脂的脂质过氧化是诱发细胞铁死亡的关键因素，华中科技大学同济医学院的袁萍将肿瘤细胞抑制脂质过氧化和抵抗铁死亡的研究进展呈现在“癌症中与脂质过氧化相关的铁死亡抑制机制”一文中。脂代谢的表观遗传调控机制是本领域的新兴热点研究主题，尤其是对众多长非编码RNA以及环状RNA是否对脂代谢具有调控作用还不知晓。延安大学生命科学学院王晓涧在“长非编码RNA CASC15影响肝细胞SREBP1a表达及定位”的研究论文中揭示CASC15通过促进SREBP1a前体蛋白质表达以及向核内转位的方式影响肝细胞脂肪酸合成。山西农业大学动物科学学院的李步高发现猪环状RNA分子circECH1具有抑制前体脂肪细胞增殖功能，相关研究成果在“CircECH1 inhibits proliferation of porcine preadipocyte by sponging miR-365-5p”论文中展示。

脂代谢的生理和病理性改变是复杂的调控过程。希望通过本专栏的文章，让读者对血浆脂蛋白代谢、某些疾病状态下脂代谢过程的改变有更加深入的认识，并以此为基础在脂代谢领域做出突破性研究成果，为治疗脂代谢紊乱相关性疾病提供更多更好的干预靶点。

Surf4 is a member of the Surfeit gene cluster. It is widely expressed and localized in endoplasmic reticulum. As a cargo receptor, Surf4 participates in the transport of proteins between the endoplasmic reticulum and Golgi apparatus. It is newly discovered that Surf4 participates in the transport of apolipoprotein B, thus affecting the transport of very low density lipoprotein precursors. It plays a regulatory role in VLDL secretion. Knockout of liver Surf4 can significantly reduce plasma total cholesterol and triglyceride levels without inducing liver lipid accumulation and pathological changes. These results suggest that Surf4 may be a potential drug target and has potential value in the diagnosis and treatment of cardiovascular diseases. In this paper, the main physiological functions of Surf4, especially the transport function of apolipoprotein B transport between endoplasmic reticulum and Golgi apparatus as a transport receptor, as well as the research progress of its involvement in the regulation of lipid metabolism and related diseases, are systematically expounded. This paper can also improve in-depth research of Surf4 and its potential application as a new method of lipid-lowering therapy for hyperlipidemia patients.

Obesity is a global health problem. One third of the adult population in the world is overweight or obese, and the proportion of obese children is also increasing year by year. In addition, overweight or obese people are vulnerable to serious chronic diseases, such as type II diabetes, hypertension, cardiovascular disease and asthma. Increasing evidence shows that chronic inflammation is an important feature of obesity, and persistent inflammation can lead to obesity or related metabolic diseases. Therefore, obesity is now considered as a low-grade chronic inflammatory disease associated with metabolic disorders. Understanding the relationship between immune cells and fat deposition may be of great significance for developing therapeutic strategies for obesity and related metabolic diseases. Macrophages are the most abundant immune cells in adipose tissues and play an important role in the induction and regression of inflammation. This review summarizes the response of macrophages in adipose tissues in obesity, and the regulatory mechanism of macrophages on adipocytes, which then affects the occurrence and development of obesity. We also summarize four main ways for macrophages for obesity regulation: macrophages reduce or increase fat deposition by interfering with the expression of PPARg or Nadk in adjacent adipocytes by secreting exosome; macrophage polarization between M1 and M2 types cause changes in fat deposition; macrophages regulate lipid deposition by secreting regulatory factors that cause changes of sympathetic nerve fibers in adipose tissues; macrophages regulate lipid deposition by capturing exogenous mitochondria. Thus, the change of macrophages in obesity is a key event and understanding its regulatory mechanism may be a new direction of obesity treatment in the future.

Lipoproteins, as water-insoluble lipid carriers in the blood and playing an important role in lipid transport and metabolism, are a complex class of spherical particles composed of cholesterol esters, triglycerides, apolipoproteins, phospholipids and free cholesterol. Lipoproteins could be classified as high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, intermediate-density lipoprotein and chylomicrons according to their particle size, density and apolipoprotein composition. Furthermore, depending on the isolation technique, lipoproteins can be further subdivided into different subclasses with different functions. In traditional clinical testing, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and apolipoproteins are used as routine indicators to evaluate the risk, progression and treatment effects of various types of cardiovascular diseases. However, in recent years, as the study of the function of lipoproteins and their subclasses has been intensified, conventional indicators no longer meet the need for accurate prediction and efficient treatment of cardiovascular diseases. Therefore, the search for more reliable evaluation indicators has become particularly important. The study of the function of lipoproteins and their subclasses will be the key to solving this bottleneck, which will help to treat cardiovascular diseases such as hyperlipidemia and atherosclerosis caused by abnormal lipid metabolism. In addition, it is also a prerequisite to broaden its application in the fields of nutrition, metabolism and disease research. In recent years, lipoprotein subclasses have been a hot topic of research, and new functions have been discovered in addition to lipid transport and metabolism. In this paper, by reviewing and prospecting the roles of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein and chylomicrons in lipid metabolism in vivo, the reference for the functional studies of lipoprotein subclasses in nutrition, metabolism and diseases will be provided.

Ferroptosis is a kind of cell death that features iron-overload and lipid peroxidation. It is different from apoptosis and other cell death pathways. Recent investigations revealed that it is possible to induce or promote ferroptosis to eradicate tumors. But in some kinds of tumors, cancer cells are less sensitive and even resist ferroptosis. Besides, multiple cancer cells are resistant to ferroptosis inducers during the preclinical experiments, which causes considerable concerns. So it will be a great help for the cancer treatment to clarify the mechanisms why cancer cells resist ferroptosis, explore the possible targets and suppress cancer resistance to ferroptosis. It is known that ferroptosis consists of reactive oxygen species (ROS) production, lipid peroxidation, plasma membrane damage and cell death. Lipid peroxidation of plasma membrane is the core of ferroptosis execution, which plays a decisive role in the plasma membrane integrity and the cell fate. Focusing on the critical event, this review will introduce how it develops and possible mechanisms of its leading to cell deaths, and summarize the research progress on mechanisms that cancer cells resist ferroptosis through limiting lipid peroxidation from four aspects: membrane phospholipid composition, oxidation cascade reaction, elimination of lipid peroxides and repairment of impaired plasma membrane. We envision that it will promote a bettering understanding of tumor treatment effects and provide clues for drug treatments for ferroptosis-sensitive tumors and drug-resistant cancer cells.

The long non-coding RNA CASC15 (CASC15) is considered as a tumor-related lncRNA involved in regulating biological processes such as proliferation, invasion and migration of a variety of tumor cells. However, the role of CASC15 in intracellular lipid metabolism remains unclear. The sterol-regulatory element binding proteins 1 (SREBP1) is a key transcription factor that regulates lipid metabolism in cells, and its member SREBP1a mainly regulates the expression of key enzyme genes in lipid synthesis. In this paper, we investigated the effects of CASC15 on the expression and localization of lipid regulator SREBP1a in human liver cells through molecular biology and cell function experiments. The results showed that in liver cells, the mRNA and total protein levels of intracellular SREBP1a remained unchanged after overexpression of CASC15 (P<0.001), while the precursor protein levels increased (P<0.05) with enhanced translocation into the nucleus; However, the levels of fatty acid synthesis-related products free fatty acids (P<0.001) and triglycerides (P<0.001) regulated by SREBP1a showed a down-regulation trend. This paper reveals a possible mechanism by which CASC15 regulates lipid metabolism in liver cells, hoping to provide new ideas for the treatment and research of diseases related to lipid metabolism disorders.

Circular RNA (circRNA) is a covalently closed RNA and plays an important role in fat metabolism. This study was conducted to explore the regulation effect of circECH1 (circular RNA enyl CoA hydrase 1, circECH1) on preadipocyte proliferation. In this study, with quantitative real-time PCR (qRT-PCR) analysis, Sanger sequencing, and RNase R digestion assay, circECH1 was proven to be capable of stable ring formation. It was expressed in all tissues of Mashen pig and its expression in adipose tissue increased with age. Functional studies showed that the expression of proliferation related genes (PCNA, CDK1 and MKi67) and the number of proliferating cells were significantly increased after circECH1 interference (P<0.01). In order to further explore the molecular mechanism, miRDB, miRWalk and RNAhybrid software were used to predict the downstream target miRNAs and genes of circECH1, and dual-luciferase reporter gene and RNA-binding protein immunoprecipitation assay revealed that circECH1 directly targeted miR-365-5p. Proliferation related genes (PCNA and CDK1) and the number of proliferating cells were significantly increased after overexpression of miR-365-5p in porcine preadipocyte (P<0.01). After transfected with miR-365-5p inhibitor, proliferation related genes (PCNA, CDK1and MKi67) and the number of proliferating cells were significantly decreased (P<0.01). In addition, after co-transfection with si-circECH1 and miR-365-5p inhibitor, compared with independent transfection with miR-365-5p inhibitor, both the expression of proliferation related genes (PCNA, CDK1 and MKi67) and the number of proliferative cells was significantly increased (P<0.01). The results of this study proved that circECH1 exists in porcine adipose tissue and regulates the proliferation of porcine preadipocyte by adsorption of miR-365-5p. The present study provides a theoretical basis for further understanding the molecular mechanism of porcine preadipocyte proliferation.

长久以来，我们“顾名思义”，“理所当然”地认为核糖核酸酶A的功能就是降解核糖核酸（RNA）。事实上，随着研究的深入，发现该家族不少成员不仅能降解RNA，而且能精准地在特定位点切割RNA产生功能性非编码RNA，甚至具有“非酶”功能！例如，我们课题组研究的核糖核酸酶A超家族成员5（ribonuclease 5，也称angiogenin，中文译为“血管生成素”）不仅以酶的形式参与RNA代谢（主要是rRNA、tRNA和miRNA），而且能以转录因子的方式促进rRNA转录、以细胞因子的方式调控细胞行为、作为细胞内分子机器的一个成员与蛋白质相互作用；不仅是一个应激响应蛋白质，而且在维持细胞/组织稳态中发挥重要作用。因此，在《中国生物化学与分子生物学报》编辑部的支持下，本专栏邀请了国内从事核糖核酸酶A研究的专家，结合自己的研究专长，分别从核糖核酸酶A超家族的研究历史、发挥多种生物学功能的结构基础、在肿瘤发生发展中的作用、抗微生物作用、活性检测方法等角度系统综述了该家族的研究进展，并在同一实验条件下系统评估了该家族在人体中的8个典型成员的抗菌活性。 首先，本课题组回顾了核糖核酸酶A超家族的研究历程，探讨了未来的研究方向，特别呼吁要系统研究该超家族成员除降解RNA外的其他生理病理功能；为吸引大家的关注，特别将文章题目定为“核糖核酸酶Ａ超家族：不仅仅是一组降解RNA的酶”。其次，为帮助读者更好地理解该家族成员发挥不同作用的原因，邀请从事人源核糖核酸酶A免疫调节研究的四川农业大学陆路副教授撰写“人核糖核酸酶Ａ家族生物学功能的结构基础”，概述了决定家族成员酶活性、抗微生物特征、免疫调节等生物学功能的结构基础。近年来，美国德州大学安德森癌症中心的洪明奇教授、塔夫茨大学的胡国富教授等团队相继报道了核糖核酸酶A超家族成员1、4、5、7等在不同肿瘤中的作用，引发了学术界的兴趣。为此，本专栏邀请在tiRNA等非编码RNA与肿瘤领域有深厚造诣的宁波大学郭俊明教授全面综述了“核糖核酸酶Ａ家族典型成员在肿瘤发生中的作用”。为深入理解该超家族成员对微生物的杀伤活性及内在机制，本专栏邀请长期从事微生物与宿主相互作用、最近专门研究家族成员1、2、5与先天免疫关系的哈尔滨医科大学张凤民教授撰写“人核糖核酸酶Ａ超家族抗微生物活性及其作用机制”，对各成员的抗微生物（包括病毒、细菌、真菌）和抗寄生虫活性及其作用机制进行系统综述，并展望了其作为抗微生物活性物质和天然免疫分子在治疗严重和耐药微生物感染中的应用前景。为帮助读者系统了解当前的核糖核酸酶A活性检测方法，邀请创新研发了多种新型检测技术的湖南大学刘斌教授撰写“RNase A活性检测及其在癌症靶向治疗中的应用”，不仅介绍了基于传统技术的酸溶法、凝胶电泳法、电化学法方法和液滴微流体法，而且全面总结了基于荧光探针技术的新型活性检测方法。最后，考虑到当前世界各实验室对该家族成员的抗菌活性报道不一致，安排浙江大学的盛静浩副教授组织队伍，在同一实验条件下以半致死浓度评估了人源8个典型成员对革兰氏阴性菌和革兰氏阳性菌的抗菌活性，为正确认识该家族的抗菌活性提供了参考。 希望通过本专栏的文章，让大家更全面地认识核糖核酸酶A超家族成员的功能及其在临床诊疗、甚至疾病预警预防的应用前景，吸引更多的研究者投入到相关领域的研究中，以期全面、深入地解析该家族成员的生理病理功能。

The RNase A superfamily, also known as the vertebrate secreted ribonucleases superfamily, is the most extensively studied ribonuclease family in the fields of protein structure, enzymology and molecular evolution of the 20th century. Since the first member was isolated from the bovine pancreas in the early of last century, thousands of members have been identified from hundreds of vertebrates, including mammals, amphibians, reptiles, birds and fish. The early research on the members of this family has not only promoted the development of protein chemistry technology, but also set a foundation for the modern biological research. So far ithas been known that the human RNase A superfamily includes 8 canonical members (RNase 1 ~ RNase 8) and 5 non-canonical members (RNase 9 ~ RNase 13). In terms of their functions, it was once thought that the members of the family only degraded RNA. With the discovery of angiogenin (RNase 5), eosinophil-derived neurotoxin (EDN; RNase 2) and eosinophils cationic protein (ECP; RNase 3), it has been realized that other functions exist, which are either dependent or independent on their catalytic activity, including host defense, immunomodulation, angiogenesis, antitumor activity and so on. However, our understanding of the functions of these members remains incomplete. Herein, we review the research history of the RNase A superfamily and discuss the future direction with emphasis on their non-RNA degradation functions under both physiological and pathological conditions.

The human ribonuclease A family consists of 13 members, namely RNase1-RNase13. They share high sequence similarity and most of them contain 6~8 cysteine and form intramolecular disulfide bonds to maintain the unique spatial structure. Among them, of which RNase1-RNase8 has a variety of biological activities and can be summarized into three categories: involved in the cleavage, modification and degradation of RNA after transcription; Has antibacterial, antifungal and antiviral activity; and immunomodulatory effects, while RNase9-RNase13 has no ribonucleolytic activity. In this paper, we have reviewed the recent structural and functional progresses of RNaseA family proteins, with an emphasis on the structural determinants in order to guide the development of RNaseA-based antimicrobial drugs and the investigation of RNaseA in host immunity.

In human, the ribonuclease A (RNase A) family contains 8 canonical members (RNase 1-RNase 8). Research evidence indicated that all the canonical members of this family, except RNase 8, are involved in the occurrence and development of a variety of tumors, including pancreatic cancer, colorectal cancer, bladder cancer, breast cancer, and skin cancer, etc. During tumorigenesis, the expression of specific RNase increased and glycosylation modifications changed, which are potential markers for tumor diagnosis; They also participate in tumor initiation, growth, and metastasis with a variety of mechanisms, and are potential targets for tumor therapy; Meanwhile, some members have the function of killing tumor cells and inhibiting tumor development, and it is possible to develop into tumor therapeutic drugs. Concretely, RNase 1 suppresses tumor growth by directly killing tumor cells or reducing local inflammation through its ribonuclease activity-dependent cytotoxicity and extracellular RNA degradation functions; however, its binding and activation of ephrin A4 signaling pathway promotes breast cancer initiation. RNase 2 and RNase 3 are important components of eosinophil granule proteins that play an important role in anti-tumor immune defense, and their function of killing tumor cells depends on both cationic nature and ribonuclease activity. RNase 4 and RNase 5 can promote tumorigenesis by inducing angiogenesis, promoting tumor cell proliferation, and inhibiting tumor cell apoptosis. The molecular mechanisms of RNase 5 action include promoting the transcription of 47 S precursor rRNA, activating signaling pro-tumor growth signaling pathways, and generating tRNA-derived stress-induced RNA (tiRNA). Besides, RNase 6 and RNase 7 are related to the occurrence of tumors thought their specific role and mechanism are still unclear. In this review, we summarized the relevance and mechanism of RNase A family members on promoting or inhibiting tumors and analyzed their clinical application potentials.

Human RNase A (human RNase A) superfamily contains 13 members (RNase 1~RNase 13) with different biological activities. In addition to the conserved catalytic sequence, its protein structure also has a significant diversity of sequences, which determines that human ribonuclease A can exert biological functions other than ribonuclease activity. Human RNase A superfamily members are expressed in various immune cells such as eosinophils, neutrophils, monocytes, and macrophages and can be secreted to exert various biological functions, including anti-microbial activity, promote host defense, participate in angiogenesis and sperm maturation, etc. Some members of the human ribonuclease A superfamily can exert antimicrobial and antiparasitic activities through direct actions such as hydrolysis of viral RNA, inhibition of viral replication, destruction of bacterial cell walls, promotion of microbial aggregation, damage to parasitic cell membranes and mitochondrial membranes, and indirect actions mediated by host innate immune cells, thereby participating in host defense. This article reviews the antimicrobial (including viruses, bacteria, and fungi) and antiparasitic activities of human ribonuclease A and their mechanisms of action. It also prospects the prospects of human ribonuclease A as an active antimicrobial substance and innate immune molecule for the treatment of severe and drug-resistant microbial infections.

The RNase A family members are involved in various physiological and pathological processes such as cell proliferation, survival, development, differentiation, migration, and invasion. Because the RNase A activity and protein expression levels in humans are closely related to the development of pancreatic, ovarian, bladder, and thyroid cancers, therefore accurate monitoring of RNase A levels can help to elucidate the molecular mechanism of tumor pathogenesis, drug screening, clinical diagnosis, and prognosis assessment. In addition, the RNase A family can specifically hydrolyze cytosine (C) or uracil (U) residues of RNA, which can effectively kill tumor cells and inhibit HIV-1 virus replication, thus RNase A has the function of killing tumor cells by lysing intracellular RNA molecules and inducing apoptosis, which is a promising class of anti-tumor protein drugs. Nanotechnology-based delivery of RNase A with therapeutic functions to specific target sites of cells to achieve the anti-tumor function of protein-targeted therapy has shown good application prospects. This paper focuses on the existing activity assays of RNase A and its application in targeted therapeutic-related diseases, aiming to provide a reference for utilization of RNase A in clinical applications and targeted drug screenings.

Antimicrobial peptides, which hold a broad spectrum of bactericidal effects, are important immune defense molecules of the human body. Ribonuclease A is a vertebrate-specific secretory protein that has eight members (RNase1-8) in the human proteome. As an important class of antimicrobial peptides, they are widely distributed in the tissues that need to resist pathogenic microorganisms, and all of them have certain antimicrobial activities in addition to their own unique biological functions. However, reports on their antibacterial activities are not consistent from various laboratories, thus a cross-sectional comparative analysis is needed. To this end, we expressed and purified recombinant proteins of eight classical members of the human ribonuclease A superfamily, and evaluated their antibacterial activities against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria with 50% lethal concentrations under the same experimental condition. The results showed that the 50% lethal concentrations of recombinant RNase1-8 proteins against Escherichia coli were 0.081¹, 0.046, 0.008, 0.250, 2.028, 0.072, 0.001 μmol·L^-1 and 1.1416 μmol·L^-1, respectively; that against Staphylococcus aureus were 3.427, 1.856, 2.211, 5.188, 8.274, 4.356, 2.502 μmol·L^-1 and 9.916 μmol·L^-1, respectively. The results indicate that there is a significant difference in RNase1-8 antibacterial activities against Escherichia coli, among which RNase3 and RNase7 were most active, and both of them had significantly higher antibacterial activities than their activities against Staphylococcus aureus. Meanwhile, there were no significant differences in their antibacterial activity against Staphylococcus aureus. Therefore, we conclude that the Ribonuclease A superfamily has a higher killing activity against Gram-negative bacteria, and may have the potential to be further developed as antibacterial products.

Organoid construction and culture technology opens a new frontier in biomedicine in recent years, which has been widely applied in the fields of tissue and organ development, disease pathogenesis, drug development and regenerative medicine. The core technique of organoid construction and culture is established according to the mechanistic studies about different tissue and organ development in vivo. A three-dimensional (3D) microenvironment consisting of extracellular matrix components and multiple cytokines is designed and constructed to support stem cell proliferation and differentiation. Based on the specific 3D microenvironment, stem cells and their differentiated cells can form self-organizing organoids resembling small units of the organ of origin in structure and function. Although the construction and culture technologies of various types of organoids have been widely used, there are still many technical challenges, such as the complexity of manipulation, the uncertainty of the yields of organoids, and structural and functional differences between organoids and real tissues. The development of advanced biofabrication technologies has promoted the improvement of organoid culture systems. In this review, we focus on the research progress of 3D microenvironment constructed by matrix components and cytokines and discuss the application of advanced biofabrication technologies in organoid construction and culture. Microwell-based cultural technology has been used to control organoid development and generate organoids in similar size and function. Micropatterning-based organoid platforms enable stem cells definitively proliferate and differentiate into functional cells in response to micropattern design and can accurately control organoid formation. 3D bioprinting technology can be used to build blocks in bioprinted 3D models reproducing the cellular variety and cytoarchitecture of real tissues. It remains a great challenge to improve the organoid culture systems and generate multiple organoids resembling the actual tissues or organs. The convergence of organoid culture and biofabrication technologies may help improve the utility of organoids in research and therapeutic applications.

Protein ubiquitination, as one of the main protein post-translational modifications in eukaryotic cells, mediates the specific intracellular protein degradation through the ubiquitin - proteasome system (UPS), as well as broadly participates and regulates almost all living processes including gene transcription, signal transduction, DNA damage and repair, cell cycle, stress response, and immune response. The precise regulation of the UPS constitutes a stable and complex ubiquitination signal network, and the disorder of ubiquitination usually causes the occurrence and development of cancer, neurodegenerative diseases, metabolic diseases and other diseases. In recent years, proteomics based on mass spectrometry (MS) has gradually matured and greatly promoted the depth and breadth of ubiquitination modification research. Relying on ubiquitinated protein/peptide enrichment technology development and upgrading of high-throughput, high-coverage and high-sensitivity of mass spectrometry detection platform, the ubiquitinomics is rapidly developed and used to describe the protein ubiquitination map, which has been widely used in the research and mechanism exploration of ubiquitination proteome in human pathophysiology. In this paper, ubiquitinated protein/peptide enrichment methods, mass spectrometry identification techniques, quantitative labeling techniques and data processing methods, as well as existing problems and challenges in the research of ubiquitinomics are reviewed. Meanwhile, the applications of ubiquitinomics techniques in diseases research are reviewed, which provide a reference for the discovery and identification of ubiquitin modification proteins, and ideas for the screening of drug targets and therapeutics of related diseases.

Free editing of genomic DNA has long been a biologist’s dream, and with the discovery and application of a powerful gene-editing tool called CRISPR-Cas9, that dream is coming true. At first, several CRISPR-Cas systems such as Cas9, Cas12a and Cas12f were found to be used for eukaryotic DNA editing. Subsequently, RNA-targeting nucleases such as Cas13a, Cas13b and Cas13d were discovered successively. In addition, a variety of new CRISPR-Cas systems have been engineered with higher DNA-cutting activity, greater specificity and smaller sizes than the natural CRISPR system. These artificially engineered CRISPR-Cas systems form a powerful tool set for DNA sequence knockout, base replacement, epigenetic editing, and even activation and suppression of gene expression. CRISPR gene editing technology is not only a powerful tool for gene function research, but also shows great potential in the discovery of therapeutic targets for diseases, nucleic acid diagnosis of pathogens, clinical treatment of tumors and other diseases. Of course, many potential problems need to be solved in practical application of CRISPR, such as efficient delivery system in vivo, immunogenicity, off-target effect and so on. These issues will be discussed in this review. We believe that with the further improvement of CRISPR editing technology, it will play a greater role in the prevention and treatment of human diseases in a more perfect and precise manner.

The formation and maintenance of the spatial conformation of eukaryotic chromatin are jointly regulated by a variety of factors, among which many proteins play an important role in the formation and maintenance of the three-dimensional (3D)structure of chromatin, and the specific mechanism of action of a large number of proteins in the 3D genome remains to be researched. Here, we discussed research techniques, ideas, and prospects, respectively. Firstly, we summarized the current research techniques for 3D chromatin structure-related proteins. Techniques based on fluorescence microscopy include structured illumination microscopy, single-molecule localization microscopy, and stimulated emission depletion microscopy, which can improve the imaging resolution of chromatin 3D structures and enables more detailed imaging of chromatin 3D structures. Sequencing technologies include chromatin co-immunoprecipitation sequencing technology for transcription factors, chromatin conformation capture technology for chromatin and related technologies. Then, we introduced how to discover 3D chromatin structures based on co-localization and ideas to study related mechanisms based on which we classified, as well as how to study the mechanism of action of proteins related to the 3D structure of chromatin. Mechanisms identified so far include directly acting on deoxyribonucleic acid, cooperating with cofactors, mediating phase separation, participating in ring extrusion, co-operating with non-coding ribonucleic acid, causing chromatin modification and G-quadruplex correlation, etc. Finally, we discuss the challenges and future development trends of existing research technologies, and point out the improvement direction of existing research technologies to promote the development of 3D genomics research at the molecular level, in terms of the experimental process, cost, and bias.

Mesenchymal stem cells (MSCs) are a kind of adult stem cells capable of self-renewal and multiple differentiation, they can derive from multiple tissues. After transplantation, MSCs can migrate and home to the sites of damaged tissues. By secreting immunomodulatory factors, cytokines, growth factors, extracellular vesicles and other bioactive substances, they play the roles of anti-inflammatory, anti-viral, anti-apoptosis, anti-fibrosis, promotion of angiogenesis and immune regulation. They have shown good efficacy in the treatment of autoimmune diseases and promote tissue and organ repair. At present, more than 10 MSC products have been listed in the world, and more than 20 MSC drugs have been acquiesced in clinical trials in China. Extracellular vesicles are bilayer lipid particles secreted by cells and derived from the membrane system. They carry bioactive substances of parent cells, including proteins, lipids, mRNA and cytokines, and can transmit parent cell signals to recipient cells. Therefore, extracellular vesicles derived from MSCs have biological characteristics similar to their parent MSCs. Because of its small size, low immunogenicity, strong tissue permeability, long cycle half-life, high stability and low risk, it has attracted more and more attention as a non-cell therapy product in recent years. In addition to the functions of tissue development and function maintenance, immune regulation, anti-oxidative stress and promoting regeneration, MSCs and their extracellular vesicles can also be used as biological carriers to deliver bioactive substances, therefore playing an important role in the process of anti-tumor and tissue repair. The review provides an overview of function of the MSCs and their extracellular vesicles, and the research progress of MSC extracellular vesicles as drug carriers.

Circadian clock is a mechanism that organisms evolved to adapt to the day-night alteration caused by the 24-hour-period of earth self-rotation. From photosynthesis and leaf opening-closing of plants to sleep-wake, feeding, metabolism, hormone secretion, and body temperature fluctuation of mammalians, are all under control of the circadian clock. Generally, endogenous rhythm is relatively stable and has the temperature compensation effects. Central clock is synchronized by external light conditions, and the rhythms of peripheral tissues are affected by the metabolism of the body’s own feedback. However, in certain extreme circumstances, such as the polar regions where constant darkness or light maintains for months, the plateaus where oxygen content is low and the temperature changes dramatically throughout the day, arid desert areas with a wide range of temperature variations between day and night, lightless deep-sea, and even the space far away from the Earth, other environmental factors besides light can also affect the circadian clock of the organisms. In this review, we discuss the molecular mechanisms by which light, hypoxia and temperature influence circadian clock, and summarize the effects of light, oxygen and temperature on circadian clock in the polar, plateau, desert, deep-sea, and space at individual and molecular level. These studies may help us to a better understanding on how organisms adapt to extreme environments, and provide more information for people who need to work in extreme environments to adjust their sleep and physical states.

A biomarker is a measurable change associated with the biological process (including continuously from the healthy stage to the disease stage). According to the theory of homeostasis, urine accumulates all kinds of early changes of the body, so we can find subtle changes at the very beginning of the disease development. As urine is the better source of the next-generation biomarkers, urine biomarker studies are expected to greatly promote the development of medical technologies such as human disease diagnosis, prevention, treatment, or prognosis. However, the components found in clinical samples of urine are not only related to the disease, but also associated with many other confounding factors. Using animal models, we can eliminate interfering factors caused by medicine and other lifestyle factors and we can also study early biomarkers even before the earliest clinical symptoms appear. In biomarker studies of human samples, the effects of confounding factors such as therapeutic drugs must be considered. To discover small early changes in disease, pre-and-post control of the same person can minimize most interfering factors. The combined method of urine proteomics and one-to-many analysis can be applied to the exploration of any unknown disease. One-to-many analysis means a comparative analysis of one sample to many controls. In this way, changes in urinary proteins before, during and after disease and/or treatment can be found, which can provide useful information for early detection and evaluation of the disease condition and treatment effect. To sum up, the recognition of urinary biomarkers will require the support of the policy and ethical principles, the cooperation of more doctors and patients and the participation of more foundations and companies. This review focuses on the concepts, theoretical ideas, research status, methods and technologies, and prospects of urine biomarkers and urine proteomics.

Chromatin accessibility is one of the important indicators to evaluate the stability of chromatin structure, which is used to evaluate the binding ability of chromatin binding factors to chromosome DNA. It plays an important role in different nuclear processes, including gene transcription regulation and DNA damage repair. Abnormal regulation of chromatin accessibility is closely related to the occurrence and development of a variety of diseases, including tumors and neurodegenerative diseases. Therefore, exploration of this attribute has become a hot spot in the field of life science and disease. More and more new technologies came into being, such as chromatin conformation capture, high-throughput sequencing, and the combination of these two technologies. With the progress of technology, more and more factors involved in the regulation of chromosome accessibility have been found and summarized, including nucleosome occupation, histone modification and non-coding RNA. A number of large-scale genomic data have drawn the chromatin accessibility map of a variety of diseases, which provides data support for revealing the relationship between the occurrence and development of diseases and chromatin accessibility. Meanwhile, with the development of single-cell chromatin accessibility sequencing technology, the investigation for division of cell types at chromatin level was achieved, which makes up for the deficiency of solely relying on gene expression for cell type division. This review will explain the development and prospect of the research about chromatin accessibility from the aspects of chromatin composition and accessibility, factors affecting chromatin accessibility, detection methods of chromatin accessibility, and its roles in cancer, briefly.

Immune checkpoints represent a group of inhibitory receptor molecules that are expresses in the surface of immune cells and play a pivotal role in maintaining immune homeostasis. In recent years, several key immune checkpoint molecules such as CTLA-4 and PD-1, has been found to exist in some kinds of tumor cells. These ectopic expressed checkpoint molecules are named as “cancer cell-intrinsic immune checkpoint molecules”. Although our understanding on cancer cell-intrinsic immune checkpoint molecules is quite limited, emerging evidence suggests that the expression and the biological functions of such molecules in different types of cancer cells are heterozygous and diverse. In particular, the discovery of “adaptive immune-independent” regulation on cancer cell behaviors would potentially benefit to design a customized cancer immune therapy, as well as to develop new therapeutic strategies for cancer. In this review, we will briefly describe the timeline of the studies, deeply discuss the complicated biological functions and the regulatory mechanisms (CTLA-4 and PD-1 as representative examples). And finally we put forward a research perspective on cancer cell-intrinsic immune checkpoint molecules. This review aims to present and promote the studies of cancer cell-intrinsic immune checkpoint molecules to the broad scientific community.

Ubiquitination is a unique protein post-translational modification in eukaryotic cells. It regulates a variety of physiological processes, such as protein homeostasis, cell cycle, immune response, DNA repair, and vesicle transport. In view of the importance of ubiquitin in live cells, pathogens have derived a series of effector proteins targeting the host ubiquitin process in the long-term evolutionary process, aiming to regulate the ubiquitin process in the host and render an internal environment suitable for the growth and reproduction of pathogens. Legionella pneumophila is a gram-negative bacterium that is responsible for Legionella pneumoniae pneumonia, causing fever and lung infection with a fatality rate of 15%~30% in severe cases. The Dot/Icm type IV secretory system is the most important virulence system in the infection of Legionella pneumophila. In the process of infecting host cells, Legionella pneumophila uses this secretion system to secrete more than 330 effector proteins to assist bacterial survival, proliferation and escape in host cells. Several effector proteins of Legionella pneumophila regulate the host ubiquitination process directly or indirectly. Recent studies found that some effectors can mediate non-canonical ubiquitination of host proteins, which is different from the classical ubiquitination process. Here, we introduce the latest research progress of novel ubiquitination mediated by effecting proteins of Legionella pneumophila, providing a reference for understanding the important role of ubiquitination in the pathogenesis of Legionella pneumophila.

Migrasomes are newly discovered cellular organelles generated during cell migration. The process to generate migrasomes is named migracytosis. Migracytosis and migrasomes function in long term intracellular communications and are shown to be essential in zebrafish embryonic development. In this review, we summarized the current research progress on migrasome, including the molecular mechanisms involved in migrasome biogenesis and its physiological significance. We also reviewed the established protocols and tools for migrasome studies, which may help setting up standard in migrasome field. In addition, we proposed the unsolved questions and potential directions of this emerging field, hoping more scientists from other field to be interested and to work on migrasomes.

So far, researchers have found more than one hundred different kinds of chemical modifications on RNA. Most of these modifications are distributed on high abundant non-coding RNAs and are important for maintaining the functions of these non-coding RNAs. In recent years, thanks to the application of highresolution mass spectrometry and the development of whole-transcriptome sequencing technologies, more and more modifications on mRNA have been discovered, and accurately mapped and localized, including N6-methyladenosine (m6A), N6,2-O-Dimethyladenosine (m6Am), 5-methylcytosine (m5C), inosine (I), pseudouridine (Ψ), N1-methyladenine (m1A), 2′-O-methylation (Nm), N4-acetylcytosine (ac4C) and N7-methylguanine (m7G), etc. Among them, m6A is the most abundant internal modification in eukaryotic mRNA. The identification of its modifying enzymes, recognition proteins, and the discovery of its extensive biological functions have set off an upsurge in the study of ost-transcriptional modifications on mRNA, thus promoting an emerging research field, i.e. Epitranscriptomics. Although our understanding of these reversible and dynamic chemical modifications has just begun to take shape, there is no doubt that a new era of research on genetic information regulation has arrived. This review focuses on the three types of epitranscriptome modifications, namely m6Am, m1A, and pseudouridine—that have been studied by our group. It provides an in-depth introduction to its distribution, function, and high-throughput detection technology, and aims to provide a better understanding of related fields and a window into the flourishing development of the epitranscriptomics.

Dynamic ubiquitination in eukaryotes either enters proteins into the 26S proteasome degradation pathway or functions in signal transduction, and therefore regulates protein stability, localization and activity, thus participates in transcription, cell cycle, inflammation, tumor, immunity and other functions. Ubiquitination modification is a reversible process, which is regulated by ubiquitin ligases (E3s) and deubiquitylases (DUBs). DUBs mediate the deubiquitination of substrate proteins, regulate protein functions, and participate in various cellular processes. The protein abundance, localization and catalytic activity of deubiquitylases are strictly regulated. During the occurrence and development of tumors, many important tumor-related proteins are regulated by deubiquitylases, and dysfunction of deubiquitylases also affect DNA damage repair, apoptosis, autophagy, molecular signaling pathways and chromatin remodeling, which modulate the process of cell growth, invasion and metastasis in tumors. Therefore, DUB is an important protein family involved in tumorigenesis, and is potential drug targets. Many small molecule inhibitors have been used in the research of anti-tumor treatments. This article mainly summarizes the regulation mechanism of ubiquitin molecules, ubiquitin chain specificity, and deubiquitinating enzyme system in tumors, and provides basis for the design of clinical drug targets and diagnostic indicators.

The discovery of integrator complex (INT) expanded our understanding of noncoding U-rich small nuclear RNA (U snRNA) maturation and transcriptional regulation, and has revived the research boom in related fields. This complex consists of at least 14 subunits, weighting over 1.4 MD. On one hand, it functions by the cleavage of transcripts; on the other hand, it interacts with protein phosphatase 2A (PP2A) and dephosphorylates the C-terminal repeat sequence of RNA polymerase Ⅱ (PolⅡ), thus regulating the transcriptional activity of RNA PolⅡ, and functions in the production of various RNAs (messenger RNA, small nuclear RNA, enhancer RNA, etc.). INT is recruited to the CTD during transcriptional initiation stage and moves along the U small nuclear RNA (snRNA) gene during transcription. Upon the recognition of 3′ maturation sequence element, its cleavage activity is triggered and the matured transcripts are released. Besides, it is also involved in many other processes, including protein-coding gene transcription pause-release, transcriptional elongation, regulation of enhancer RNA transcription, and DNA and RNA metabolism etc. Meanwhile, the significance of INT complex or its components in tumorigenesis, pathogenesis, and ontogeny has being gradually highlighted. Nevertheless, the structural and compositional studies just took a new breakthrough recently. The 14 subunits that make up the complex are characterized by a large number of α-helices, which are further assembled into a huge transcription regulation machine based on the formation of functional modules. This article will mainly discuss about the composition, structural characteristics, functional studies, disease-association, and problem outlook of the integrator complex.