Early embryogenesis relies on maternally inherited mRNAs. Although the mechanism of maternal mRNA degradation during maternal-to-zygotic transition (MZT) has been extensively studied in vertebrates, how the embryos maintain maternal mRNA stability remains unclear. Here, we identify Igf2bp3 as an important regulator of maternal mRNA stability in zebrafish. Depletion of maternaligf2bp3destabilizes maternal mRNAs prior to MZT and leads to severe developmental defects, including abnormal cytoskeleton organization and cell division. However, the process of oogenesis and the expression levels of maternal mRNAs in unfertilized eggs are normal in maternaligf2bp3mutants. Gene ontology analysis revealed that these functions are largely mediated by Igf2bp3-bound mRNAs. Indeed, Igf2bp3 depletion destabilizes while its overexpression enhances its targeting maternal mRNAs. Interestingly,igf2bp3overexpression in wild-type embryos also causes a developmental delay. Altogether, these findings highlight an important function of Igf2bp3 in controlling early zebrafish embryogenesis by binding and regulating the stability of maternal mRNAs.

Inflammation is critical for obesity and obesity-induced insulin resistance (IR). In this study, we reveal the function and mechanism of acarbose on adipose tissue macrophage (ATM)-mediated inflammation in obesity and obesity-induced IR. First, acarbose enhances the abundance of propionic acid-producing Parasutterella, therefore indirectly inhibiting the survival and proinflammatory function of M1-like ATMs via GPR43. Most interestingly, acarbose can directly inhibit M1-like ATM-mediated inflammation through GPR120. Diet-induced obese mice exhibit nitrobenzoxadiazoles (NBD) fluorescence-labeled ATMs, but lean mice that also orally received NBD fluorescence-labeled acarbose do not exhibit NBD fluorescence-labeled ATMs. This direct inhibition of macrophages by acarbose is validated in mouse and human macrophages in vitro. In conclusion, our study reveals that acarbose directly and indirectly inhibits proinflammatory macrophage phenotype, which contributes to the improvement of obesity and obesity-induced IR. The understanding of the immune regulatory effects of acarbose may extend its potential for further therapeutic applications.

Aquaculture environments frequently experience hypoxia and subsequent reoxygenation conditions, which have significant effects on hypoxia-sensitive fish populations. In this study, hepatic biochemical activity indices in serum and the content of major neurotransmitters in the brain were altered markedly after acute hypoxia and reoxygenation exposure in silver carp (Hypophthalmichthys molitrix). Proteomics analysis of the liver showed that a number of immune-related and cytoskeletal organization-related proteins were downregulated, the ferroptosis pathway was activated, and several antioxidant molecules and detoxifying enzymes were upregulated. Proteomics analysis of the brain showed that somatostatin-1A (SST1A) was upregulated, dopamine-degrading enzyme catechol O methyltransferase (COMT) and ferritin, heavy subunit (FerH) were downregulated, and the levels of proteins involved in the nervous system were changed in different ways. In conclusion, these findings highlight that hypoxia–reoxygenation has potential adverse effects on growth, locomotion, immunity, and reproduction of silver carp, and represents a serious threat to liver and brain function, possibly via ferroptosis, oxidative stress, and cytoskeleton destruction in the liver, and abnormal expression of susceptibility genes for neurodegenerative disorders in the brain. Our present findings provide clues to the mechanisms of hypoxia and reoxygenation damage in the brain and liver of hypoxia-sensitive fish. They could also be used to develop methods to reduce hypoxia or reoxygenation injury to fish.

Hypoxia is one of the serious stresses in fish culture, which can lead to physical and morphological changes, and cause injury and even death to fish. Silver carp (Hypophthalmichthys molitrix) is an important economic fish and widely distributed in China. MicroRNA is a kind of endogenous non-coding single-stranded small RNA, which is involved in cell development, and immune response and gene expression regulation. In this study, silver carp were kept in the closed containers for hypoxia treatment by spontaneous oxygen consumption. The samples of heart, brain, liver and gill were collected, and the total RNAs extracted separately from the four tissues were mixed in equal amounts according to the concentration. Afterwards, the RNA pool was constructed for high-throughput sequencing, and based on the small RNA sequencing, the differentially expressed microRNAs were identified. Furthermore, their target gene prediction and enrichment analyses were carried out. The results showed that a total of 229 known miRNAs and 391 putative novel miRNAs were identified, which provided valuable resources for further study on the regulatory mechanism of miRNAs in silver carp under hypoxia stress. The authors verified 16 differentially expressed miRNAs by qRT-PCR, and the results were consistent with small RNA sequencing (sRNA-seq). The predicted target genes number of differentially expressed miRNAs was 25,146. GO and KEGG functional enrichment analysis showed that these target genes were mainly involved in the adaption of hypoxia stress in silver carp through biological regulation, catalytic activity and apoptosis. This study provides references for further study of interaction between miRNAs and target genes, and the basic data for the response mechanism under hypoxia stress in silver carp.