Dear colleagues,

We are pleased to announce the publication of GIAD Volume 3 Issue 6. This is a special issue entitled Environmental Toxicology, edited by Professor Pingkun Zhou of the Chinese Academy of Military Medical Sciences, China.

Below, we provide brief summaries of the published articles.

1. MiRNA let-7i promotes radiation-induced pulmonary epithelial-mesenchymal transition by targeting IL-10 | Shenghui Zhou, Xin Liang, Zewen Sun, Xueping Li, Jiaojiao Zhu, Zhihua Yang, Xiujie Pan, Yilong Wang, Yongqing Gu & Maoxiang Zhu

Radiopulmonary fibrosis (RIPF) is a common complication of radiotherapy for thoracic tumors. Data suggest that epithelial mesenchymal transformation (EMT) has an important role in RIPF pathogenesis, but the underlying mechanisms remain unclear. Now, leveraging mouse lung tissue miRNA screening and functional analyses in alveolar type II epithelial cells (AECII), Professors Yongqing Gu, Maoxiang Zhu, and colleagues from the Beijing Institute of Radiation Medicine, AMMS, China, show that miRNA-let-7i promotes AECII cell EMT, promoting RIPF. These data provide a new target to potentially help prevent or treat RIPF.

Fig.1 Schematic showing how ionizing radiation might upregulate miR-let-7i in alveolar epithelial cells, which in turn induce EMT and subsequently RIPF via the IL-10/PI3K/AKT pathway.

放射性肺纤维化（RIPF）是胸部肿瘤放疗常见的并发症，许多研究证实了上皮间充质转化（EMT）在RIPF中起重要作用，但具体机制尚不清楚。来自中国军事科学院的顾永清教授和朱茂祥教授团队通过小鼠肺组织miRNA微阵列筛查结合肺泡II型上皮细胞（AECII）进行验证，揭示了miRNA-let-7i促进AECII细胞EMT进而引起RIPF的作用和机制，为放射性肺纤维化的预防和治疗提供了新的靶点。

全文链接：https://link.springer.com/article/10.1007/s42764-022-00089-8

2. Role of mitochondria in nuclear DNA damage response | Xipeng Zhao, Bin Chen, Lijun Wu & Guoping Zhao  

The DNA damage response (DDR) is an intracellular pathway that enables cells to perceive DNA damage and initiate a pathway of repair. The mitochondria have an important regulatory role in this process. In this review, Professor Guoping Zhao and colleagues from the Hefei Institutes of Physical Science, CAS, China, summarize the molecular mechanisms of the mitochondrial-mediated stress response to DNA damage signals, and speculate on the future research needed to improve our understanding of the role of mitochondria in the DDR.

Fig. 2 Interactions between mitochondria metabolism and the nuclear DNA damage response.

DNA损伤反应（DDR）是细胞感知DNA损伤和自我修复的细胞内途径，线粒体在其中发挥了重要的调控作用。在这篇综述里，来自中科院合肥物理科学研究院的赵国平教授团队向我们总结了有关DNA损伤信号中线粒体介导的应激反应的分子机制的最新科学文献，帮助我们更好地全面了解线粒体DDR信号网络。

赵国平教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00088-9

3. The effects of hypoxia on female reproductive system diseases | Chenglong Ma, Zhaodian Zheng, Yanqiu Shen, Jing Fang, Xinying Huang, Jiarong Guo & Huidong Zhang

Hypoxia is associated with diseases of the female reproductive system, but there are gaps in our understanding. In this review, Professor Huidong Zhang and colleagues from the Eighth Affiliated Hospital, Sun Yat-Sen University, China, summarize data explaining how hypoxia and the key transcription factor hypoxia inducible factor (HIF-1) might drive female reproductive system diseases (including cancers) by regulating cell invasion, proliferation, apoptosis, autophagy, differentiation. The authors also emphasize the role that non-coding RNAs might play in regulating cell dysfunction under hypoxic conditions. Finally, they speculate on how we might develop new approaches for early disease detection and clinical treatment.

Fig. 3 Schematic of how hypoxia and HIF-1 might regulate the progression of female reproductive system diseases by various cellular processes.

许多的研究表明，缺氧与女性生殖系统疾病密切相关。在这篇综述里，来自中山大学第八附属医院的张慧东教授向我们总结了缺氧和HIF-1通过调节各种细胞侵袭、增殖、凋亡、自噬、增殖或分化来影响包括肿瘤在内的女性生殖系统疾病，回顾了非编码RNA在缺氧条件下调节各种细胞功能障碍的作用，为女性生殖系统疾病的早期检测和临床治疗提供参考。

张慧东教授

全文链接： https://link.springer.com/article/10.1007/s42764-022-00081-2

4. Regulatory mechanisms of mechanotransduction in genome instability| Lijun Zheng, Mintao Ji, Hong Zhang & Lei Chang

The mechanical microenvironment and internal, cellular mechanical systems have important roles in ontogenesis and adult homeostasis. Unsurprisingly, therefore, these factors are closely related to many diseases, including cancers. In this review, Professor Lei Chang and colleagues from the Medical College of Soochow University, China, explain how the extracellular mechanical microenvironment, mechano-sensing receptors, cytoskeletal systems, and mechano-signaling processes underlying nuclear mechano-transduction impact on genomic instability. This review serves as an excellent resource to better understand the relationship between the mechanical microenvironment and genomic instability.    

Fig. 4 The contributions of mechanical factors on genomic instability.

机械微环境和细胞内部机械系统在个体发育和成体稳态过程中扮演着重要的角色，与包括肿瘤在内的多种疾病密切相关。在这篇综述里，来自苏州大学医学部的畅磊教授向我们介绍了细胞外机械微环境、机械感受受体、细胞骨架系统和核机械传递的机械信号如何影响基因组的不稳定性，帮助我们更好地理解机械微环境与基因组不稳定性的关系。

畅磊教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00086-x

5. Advances in DNA damage induced by environmental chemical carcinogens| Han Zhang, Wenfeng Lu, Yun Zhou & Yiguo Jiang

Chemical carcinogens are common exogenous agents that can induce DNA damage and elicit DNA damage repair procedures. Due to the different physical and chemical properties of these various carcinogens, the types of DNA damage that can be caused also differs. In this review, Professors Yun Zhou, Yiguo Jiang and their colleagues from Guangzhou Medical University summarize the mechanisms by which diverse environmental chemical carcinogens (including heavy metals, polycyclic aromatic hydrocarbons, and aromatic amines) can cause DNA damage. They also speculate on types of DNA damage these carcinogens might cause.

Fig. 5 The five main types of DNA damage.

化学致癌物是常见的外源性DNA损伤剂，会造成不同类型的DNA损伤，进而引起细胞启动DNA损伤修复程序。由于化学物质的物理化学性质不同，这些致癌物引起的DNA损伤也不尽相同。在这篇综述里，来自广州医科大学的周芸教授和蒋义国教授团队向我们总结了各种环境化学致癌物（即重金属、多环芳烃和芳香胺）对DNA的损伤和最终致癌的机制，帮助我们全面了解环境致癌物与基因组稳态之间的关系。

周芸教授

蒋义国教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00092-z

6. DNA damage mediated by UV radiation and relative repair mechanisms in mammals| Yinghui Wang, Xuyi Deng & Meijuan Zhou

Ultraviolet (UV) radiation is a common environmental pathogenic factor and is known to induce skin cancer. In this review, Professor Meijuan Zhou and colleagues at Southern Medical University, China, explain the mechanisms underlying how UV radiation can promote DNA damage. They particularly focus on cycloutene pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PPs) that form when DNA absorbs UV photons. They then discuss how the nucleotide excision repair pathway serves to excise such photolesions to enable repair of the damaged DNA strand.

紫外线辐射是诱发皮肤癌的最常见环境致病因素，在这篇综述里，来自南方医科大学的周美娟教授团队向我们总结了紫外线诱导DNA损伤的机制，并讨论了DNA损伤修复机制和几种信号转导途径协同作用的最新进展。

周美娟教授

全文链接：https://link.springer.com/article/10.1007/s42764-022-00090-1