Abstract Accurate and efficient molecular recognition plays a crucial role in the fields of molecular detection and diagnostics. Conventional trial‐and‐error‐based molecular recognition approaches have always been challenged in distinguishing minimal differences between targets and non‐targets, such as single nucleotide polymorphisms (SNPs) of oligonucleotides. To address these challenges, here, a novel concept of dynamic addressing analysis is proposed. In this concept, by dissecting the regions of the target and creating a corresponding recognizer, it is possible to eliminate the inaccuracy and inefficiency of recognition. To achieve this concept, a Dynamic Addressing Molecular Robot (DAMR), a DNA‐based dynamic addressing device is developed which is capable of dynamically locating targets. DAMR is designed to first bind to the conserved region of the target while addressing the specific region dynamically until accurate recognition is achieved. DAMR has provided an approach for analyzing low‐resolution targets and has been used for analyzing SNP of miR‐196a2 in both cell and serum samples, which has opened new avenues for effective and efficient molecular recognition.
Background: It has been reported that enrofloxacin can impair reproductive function of mammals, induces multi-generational oscillatory effects on reproduction of Caenorhabditis elegans, and disturbes endocrine system in grass carp.Objectives: This study aims to explore the effect of short-term enrofloxacin exposure on sex steroid hormones biosynthesis in Carassius auratus var. Pengze through assessing the contents of growth hormone (GH), thyroid hormone 4 (T4), estradiol (E2) and testosterone (T) in plasma, and investigating sex steroid hormones biosynthesis based on targeted metabonomics analysis, and determining expression level of some important genes, gonadotropin-releasing hormone (gnrh), gonadotropin hormone 1-β (gth1-β), gonadotropin hormone 2-β (gth2-β) and cyp19a1a in hypothalamus-pituitary-ovary axis (HPOA).Results: We found that short-term exposure of enrofloxacin disordered contents of E2 and T in plasma of fish determined by ELISA detection, T content elevation and E2 content decline, which was confirmed by the following data from targeted metabonomics analysis of plasma. The metabonomic results showed that both T and its upstream intermediate products during the process of sex steroid hormones biosynthesis in fish were increased significantly, but E2 content was decreased markedly. At the exposure 24 h of enrofloxacin, expression of gnrh in hypothalamus, gth1-β and gth1-β in pituitary were promoted. Meanwhile GH and T4 contents in plasma, two inducers of sex steroid hormones synthesis, were augmented, which indicated that sex steroid hormones biosynthesis was improved. However cyp19a1a expression in ovary was repressed, and content of estriol (E3) was upregulated. These data suggested that enrofloxacin promoted sex steroid hormones biosynthesis and conversion of E2 to estriol (E3), but inhibited the conversion of T to E2. Finally, content of E2 was declined sharply.Discussion: Animal specific antibacterial enrofloxacin is widely detectable in aquatic ecosystem, exposure of the agent can induce adverse effects on plants and animals. This study firstly evidenced induction of disruption of sex steroid hormones by enrofloxacin in fish, which indicates enrofloxacin is an endocrine disruption compound that can induce endocrine disruption of animals, including fish.
Abstract Functional imaging (FI) techniques have revolutionized tumor imaging by providing information on specific tumor functions, such as glycometabolism. However, tumor cells lack unique molecular characteristics at the molecular level and metabolic pathways, resulting in limited metabolic differences compared to normal cells and increased background signals from FI. To address this limitation, we developed a novel imaging technique termed proximity‐enhanced functional imaging (PEFI) for accurate visualization of tumors. By using “two adjacent chemically labeled glycoproteins” as output signals, we significantly enhance the metabolic differences between tumor and normal cells by PEFI, thereby reducing the background signals for analysis and improving the accuracy of tumor functional imaging. Our results demonstrate that PEFI can accurately identify tumors at the cellular, tissue, and animal level, and has potential value in clinical identification and analysis of tumor cells and tissues, as well as in the guidance of clinical tumor resection surgery.
Ferroptosis has attracted extensive interest from cancer researchers due to its substantial potential as a therapeutic target. The role of LATS2, a core component of the Hippo pathway cascade, in ferroptosis initiation in hepatoblastoma (HB) has not yet been investigated. Furthermore, the underlying mechanism of decreased LATS2 expression remains largely unknown. In the present study, we demonstrated decreased LATS2 expression in HB and that LATS2 overexpression inhibits HB cell proliferation by inducing ferroptosis. Increased LATS2 expression reduced glycine and cysteine concentrations via the ATF4/PSAT1 axis. Physical binding between YAP1/ATF4 and the PSAT1 promoter was confirmed through ChIP‒qPCR. Moreover, METTL3 was identified as the writer of the LATS2 mRNA m6A modification at a specific site in the 5' UTR. Subsequently, YTHDF2 recognizes the m6A modification site and recruits the CCR4-NOT complex, leading to its degradation by mRNA deadenylation. In summary, N6-methyladenosine modification of LATS2 facilitates its degradation. Reduced LATS2 expression promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis. Targeting LATS2 is a potential strategy for HB therapy.
Chaperonin-containing T-complex polypeptide 1 (CCT) is a molecular chaperone in the cytoplasm of eukaryotic cells involved in the correct folding and assembly of proteins, which plays an important role in cold-stress response. This study cloned two transcripts of Pinctada maxima CCT-beta composed of 1,829 bp (CCT-beta1) and 2,289 bp (CCTbeta2), respectively, using rapid amplification of cDNA ends. Both transcripts possess 105 bp of 5′ noncoding region and the same coding region, but contain different 3′ noncoding regions of 591 bp (CCT-beta1) and 131 bp (CCT-beta2), respectively. The open reading framework (ORF) consisted of 1,593 bp that encodes 530 amino acids. The CCT-beta protein has three conserved functional domains (equatorial, apical, and intermediate domains), three CCT-family signature sequences, nine conserved ATP-binding sites, one DEAD box motif, and three protein-binding sites. The CCT-beta is highly conserved, with the cDNA homologies between P. maxima and Crassostrea gigas, Danio rerio, and Homo sapiens being 90.4%, 76.8%, and 75.8%, respectively. Real-time quantitative PCR showed that CCT-beta was differentially expressed in different organs of P. maxima, with mRNA contents declining from the gill, adductor muscle, foot, labial palps, mantle, and heart to hepatopancreas. Under cold stress, CCT-beta mRNA expression in various organs increased, but the patterns of increase varied among organs. The transcriptional level of CCT-beta peaked at 6 h in the heart and hepatopancreas, and decreased significantly at 12 h. In the adductor muscle, gill, and mantle, CCT-beta mRNA increased significantly at 12 h and declined markedly at 24 h in cold stress-exposed animals. These results indicate that CCT-beta is a cold-stress response gene, but the response pattern varies among organs. Organs with low CCT-beta basal expression may be more sensitive to cold stress than the organs with relatively high basal expression content.
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