Image_1_Identification of neurohypophysial hormones and the role of VT in the parturition of pregnant seahorses (Hippocampus erectus).jpeg

Neurohypophysial hormones regulate the reproductive behavior of teleosts; however, their role in the gestation and parturition of ovoviviparous fishes with male pregnancy (syngnathids) remains to be demonstrated. In the present study, the complementary DNA (cDNA) sequences of arginine vasotocin (VT) and isotocin (IT) from the lined seahorse (Hippocampus erectus) were cloned and identified. We observed that the mature core peptides of seahorse VT and IT were conserved among teleosts. In the phylogenic tree, seahorse VT and IT were clustered independently with teleost VT and IT. The tissue distribution patterns of VT and IT were similar, and both were highly expressed in the brain, gills, and gonads. Interestingly, they were also expressed to some extent in the brood pouch. In situ hybridization revealed that VT and IT messenger RNA (mRNA) signals in the brain were mainly located in the preoptic area region of the hypothalamus. Intraperitoneal administration of the VT core peptide to pregnant seahorses induced premature parturition, stimulated gonadotropin release, increased serum estrogen levels, and decreased prolactin secretion. Moreover, VT injection upregulated the mRNA expression of the membrane estrogen receptor in the brood pouch. In summary, neurohypophysial hormones promote premature parturition by regulating estrogen synthesis through the hypothalamus–pituitary–gonad axis.</p

Additional file 2: of Complete mitochondrial genomes of eight seahorses and pipefishes (Syngnathiformes: Syngnathidae): insight into the adaptive radiation of syngnathid fishes

Statistics of the codon usage in the mitochondrial genes. (XLSX 13 kb

Additional file 5: of Complete mitochondrial genomes of eight seahorses and pipefishes (Syngnathiformes: Syngnathidae): insight into the adaptive radiation of syngnathid fishes

List of the species used in this study. (XLSX 15 kb

Additional file 3: of Complete mitochondrial genomes of eight seahorses and pipefishes (Syngnathiformes: Syngnathidae): insight into the adaptive radiation of syngnathid fishes

95% confidence interval of dating analysis. (JPG 797 kb

Additional file 4: of Complete mitochondrial genomes of eight seahorses and pipefishes (Syngnathiformes: Syngnathidae): insight into the adaptive radiation of syngnathid fishes

Selection analysis of the mitochondrial genes. (XLSX 53 kb

Bioorthogonally Activatable Autophagy-Tethering Compounds for Aptamer-Guided Mitochondrial Degradation

Although macroautophagy degradation targeting chimeras (MADTACs) have been demonstrated to be efficient in a broad spectrum from intracellular proteins to macromolecular complexes such as lipid droplets and the mitochondrion, MADTACs still face degradation of uncontrolled protein in normal cells and cause systemic toxicity, thus limiting their therapeutic applications. Herein, we employ bioorthogonal chemistry to develop a spatially controlled MADTACs strategy. Separated warheads display no activity in normal cells but can be activated by aptamer-based Cu nanocatalyst (Apt-Cu30) in tumors specifically. These in situ synthesized chimera molecules (bio-ATTECs) can degrade the mitochondrion in live tumor cells and subsequently induce autophagic cell death, which has been further demonstrated by lung metastasis melanoma murine models. To the best of our knowledge, this is the first bioorthogonal activated MADTAC in live cells for inducing autophagic tumor cell death, which may promote the development of cell-specific MADTACs for precision therapeutics by avoiding undesired side effects

Additional file 6: of Complete mitochondrial genomes of eight seahorses and pipefishes (Syngnathiformes: Syngnathidae): insight into the adaptive radiation of syngnathid fishes

Calibration points used in the divergence time analysis by BEAST List of the species used in this study. (XLSX 10 kb

Bioorthogonal Activation of TLR7 Agonists Provokes Innate Immunity to Reinforce Aptamer-Based Checkpoint Blockade

Although cancer immunotherapy based on immune checkpoint blockade has shown promising clinical responses, the limited host response rate and systemic side effects still restrict immunotherapy efficacy. To address these challenges, here, we construct an aptamer-functionalized metal–organic framework (MOF) catalyst for bioorthogonal activation of Toll-like receptors (TLR) 7 agonists and programmed death-ligand 1 (PDL1) blockade for enhanced antitumor immunotherapy. The catalyst contains ultrasmall Pd nanoparticles enabling the local activation of TLR7 agonists in native form, which results in the remodeling of the tumor microenvironment (TME). Meanwhile, the loaded PDL1 aptamers release in response to phosphate and block the PD1/PDL1 signaling pathway between T cells and cancer cells. Thus, synergy between TLR7 agonists and PDL1 blockade induces the infiltration and activation of immune cells to initiate a robust immune response, thereby simultaneously inhibiting primary and distant metastatic tumors. The immunotherapeutic effect of our design has been demonstrated in both single and bilateral subcutaneous colorectal cancer (CT26) models. In situ bioorthogonal activation of agonists may offer an alternative approach to improve the therapeutic efficacy of immunotherapy with minimized systemic toxicity. Our work will provide good inspiration for current checkpoint blockade-based immunotherapy

Additional file 1: of Complete mitochondrial genomes of eight seahorses and pipefishes (Syngnathiformes: Syngnathidae): insight into the adaptive radiation of syngnathid fishes

List of the SSRs in the mitochondrial genome of 44 teleost fishes. (DOCX 27 kb

Image_1_The Roles of the Kisspeptin System in the Reproductive Physiology of the Lined Seahorse (Hippocampus erectus), an Ovoviviparous Fish With Male Pregnancy.JPEG

The kisspeptin/GPR54 system plays a crucial role in the regulation of the reproductive axis in vertebrates. Male pregnancy and ovoviviparity are special reproductive phenomena among vertebrates. To better understand the neuroendocrine mechanisms of male pregnancy, cDNAs encoding kiss2 and GPR54 were cloned and functionally characterized from the lined seahorse, Hippocampus erectus, an ovoviviparous teleost with male pregnancy. The core mature peptide of seahorse Kiss2 is high conserved among seahorses, but unique among vertebrate Kiss orthologs. In the phylogenic analysis, the seahorse Kiss clustered with the teleost Kiss2 clade. The kiss2 transcripts were shown to be widely expressed in various tissues, notably in the brain and gonad of the seahorse, while GPR54-2 mRNA was expressed exclusively in the brain. In addition, kiss2 mRNA found in male seahorse brain tissue increased significantly at the early pubertal stage, and decreased significantly during pregnancy. Intraperitoneal administration of seahorse Kiss2-10 to sexual mature male seahorses demonstrated to stimulate lutropin β (LHβ) and follitropin β (FSHβ) release and increased serum testosterone levels. In summary, we first identified the kisspeptin/GPR54 system in an ovoviviparous fish with male pregnancy, which might be involved in the regulation of the reproductive functions of pubertal onset, gonadal development, and male pregnancy via regulating the synthesis of both gonadotropic hormone (GTH) and testosterone.</p