RNA modifications identification based on chemical reactions.

RNA modification identification is an emerging field in epigenetics due to its indispensable regulatory role in the cell life cycle. With advancements in identification methods, an increasing number of RNA modifications has been discovered, thereby driving the development of more efficient and accurate techniques for localizing modified RNAs and elucidating their functions. High-throughput sequencing approaches for modified RNA detection can be categorized into antibody-based, enzymatic-based, and chemical-labeling-based methods. Given the intrinsic chemical reactions involved in all biochemical processes, we provide a comprehensive review of recent advancements in artificial chemical labeling and transformations of ten distinct RNA modifications and their applications in sequencing. Our aim is to contribute to a deeper understanding of the mechanisms underlying these modifications. We focus on the chemical reactions associated with RNA modifications and briefly compare the advantages and disadvantages of detection methods based on these reactions. Additionally, we introduce several approaches that identify multiple modifications through chemical labeling. As the field of RNA modification research continues to expand, we anticipate that the techniques and insights presented in this review will serve as a valuable resource for future studies aimed at further elucidating the functional roles of RNA modifications in biological processes.

Imaging of Carbonic Anhydrase Level in Epilepsy with an Environment-Sensitive Fluorescent Probe.

Carbonic anhydrases (CAs) participate in various physiological and pathological activities by catalyzing the interconversion between carbon dioxide and bicarbonate ions. Under normal circumstances, they guarantee that the relevant biological reactions in our body occur within an appropriate time scale. Abnormal expression or activity alteration of CAs is closely related to the pathogenesis of diverse diseases. This work reports an inhibitor-directed fluorescent probe FMRs-CA for the detection of CAs. Excellent selectivity, favorable biocompatibility, and desirable blood-brain barrier (BBB) penetration endow the probe with the ability to image the fluctuation of CAs in cells and mice. We achieved in situ visualization of the increased CAs in hypoxic cells with this probe. Additionally, probe FMRs-CA was mainly enriched within the liver and gradually metabolized by the liver. With the help of FMRs-CA, the increase of CAs in epileptic mouse brains was revealed first from the perspective of imaging, providing the mechanism connection between abnormal CA expressions and epilepsy.

Naphthalimide Fluorescent Skeleton for Facile and Accurate Quantification of Glutathione.

Glutathione (GSH), the most prevalent nonprotein thiol in biological systems, acts as both an antioxidant to manipulate intracellular redox homeostasis and a nucleophile to detoxify xenobiotics. The fluctuation of GSH is closely related to the pathogenesis of diverse diseases. This work reports the construction of a nucleophilic aromatic substitution-type probe library based on the naphthalimide skeleton. After an initial evaluation, the compound R13 was identified as a highly efficient GSH fluorescent probe. Further studies demonstrate that R13 could readily quantify GSH in cells and tissues via a straightforward fluorometric assay with a comparable accuracy to the results from the HPLC. We then used R13 to quantify the content of GSH in mouse livers after X-ray irradiation, revealing that irradiation-induced oxidative stress leads to the increase of oxidized GSH (GSSG) and depletion of GSH. In addition, probe R13 was also applied to investigate the alteration of the GSH level in the Parkinson's mouse brains, showing a decrease of GSH and an increase of GSSG in Parkinson's mouse brains. The convenience of the probe in quantifying GSH in biological samples facilitates further understanding of the fluctuation of the GSH/GSSG ratio in diseases.

Copper/Nitroxyl-Catalyzed Synthesis of Pyrroles by Oxidative Coupling of Diols and Primary Amines at Room Temperature.

The Cu/ABNO-catalyzed aerobic oxidative coupling of diols and primary amines to access N-substituted pyrroles is highlighted (ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl). The reaction proceeds at room temperature with an O2 balloon as the oxidant using commercially available materials as the substrates and catalysts. The catalyst system is characterized by a broad range of substrates and a good tolerance to sensitive functional groups. The gram-scale experiment proves this system's practicability.

Synergistic catalysis: cobalt-catalyzed cascade reaction for the oxidative cleavage of olefins to access esters.

An efficient strategy for the oxidative cleavage of CC bonds in olefins to form esters with one or multiple carbon atoms less over heterogeneous cobalt/nitrogen-doped carbon catalyst with dioxygen as the oxidant was described. The protocol features a wide substrate range including the challenging inactive aliphatic and long-chain alkyl aryl olefins. The reactivity of the catalyst did not decrease after reused for seven times. Characterization and control experiments reveal that synergistic effects between the metallic Co nanoparticles and Co-Nx sites provide access to the excellent catalytic activity.

Thioredoxin Signaling Pathways in Cancer.

Significance: Thioredoxin (Trx) is a powerful antioxidant that reduces protein disulfides to maintain redox stability in cells and is involved in regulating multiple redox-dependent signaling pathways. Recent Advance: The current accumulation of findings suggests that Trx participates in signaling pathways that interact with various proteins to manipulate their dynamic regulation of structure and function. These network pathways are critical for cancer pathogenesis and therapy. Promising clinical advances have been presented by most anticancer agents targeting such signaling pathways. Critical Issues: We herein link the signaling pathways regulated by the Trx system to potential cancer therapeutic opportunities, focusing on the coordination and strengths of the Trx signaling pathways in apoptosis, ferroptosis, immunomodulation, and drug resistance. We also provide a mechanistic network for the exploitation of therapeutic small molecules targeting the Trx signaling pathways. Future Directions: As research data accumulate, future complex networks of Trx-related signaling pathways will gain in detail. In-depth exploration and establishment of these signaling pathways, including Trx upstream and downstream regulatory proteins, will be critical to advancing novel cancer therapeutics. Antioxid. Redox Signal. 38, 403-424.

Engineered aptamers for molecular imaging.

Molecular imaging, including quantification and molecular interaction studies, plays a crucial role in visualizing and analysing molecular events occurring within cells or organisms, thus facilitating the understanding of biological processes. Moreover, molecular imaging offers promising applications for early disease diagnosis and therapeutic evaluation. Aptamers are oligonucleotides that can recognize targets with a high affinity and specificity by folding themselves into various three-dimensional structures, thus serving as ideal molecular recognition elements in molecular imaging. This review summarizes the commonly employed aptamers in molecular imaging and outlines the prevalent design approaches for their applications. Furthermore, it highlights the successful application of aptamers to a wide range of targets and imaging modalities. Finally, the review concludes with a forward-looking perspective on future advancements in aptamer-based molecular imaging.

Ecological risk assessment of trace metals in sediments and their effect on benthic organisms from the south coast of Zhejiang province, China.

To explore the ecological risks of trace metals in sediments and their relationship with benthic organisms, 12 trace metals were analyzed and the macrobenthos were identified in the sediments collected from the south coast of Zhejiang province which belongs to the East China Sea. Spatially, the concentrations of most trace metals were high in the estuary, except for Ba and Sr. There was no obvious enrichment for trace metals, except that the concentration of Cd slightly exceeded the coastal background. The ecological risks calculated by the concentrations of Cr, Cd, Cu, Zn, Pb, and Ni in sediments showed that the methods based on sediment quality guidelines could judge the ecological risk more intuitively than the methods based on background value (PN, PLI, RI). The significant correlations between ecological risks and benthos density and biomass revealed the negative impact of trace metals at high concentrations on macrobenthic survival in sediments.

Revealing PACMA 31 as a new chemical type TrxR inhibitor to promote cancer cell apoptosis.

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis, while dysregulation of redox homeostasis is a hallmark for cancer cells. Thus, there is considerable potential to inhibit the aberrantly upregulated TrxR in cancer cells to discover selective cancer therapeutic agents. Nevertheless, the structural types of TrxR inhibitors presented currently are still relatively limited. We herein report that PACMA 31, previously reported to inhibit protein disulfide isomerase (PDI), is a potent TrxR inhibitor. PACMA 31 possesses a pharmacophore scaffold that is structurally different from the announced TrxR inhibitors and exhibits effective cytotoxicity against cervical cancer cells. Our results reveal that PACMA 31 selectively inhibits TrxR over the related glutathione reductase (GR) and in the presence of reduced glutathione (GSH). Further studies with mutant enzyme and molecular docking suggest that the propynamide fragment of PACMA 31 interacts covalently with the selenocysteine residue of TrxR. Moreover, PACMA 31 effectively and selectively curbs TrxR activity in cells and further stimulates the production of reactive oxygen species (ROS) at low micromolar concentrations, which in turn triggers the accumulation of oxidized thioredoxin (Trx) and GSSG in cells. Follow-up studies demonstrate that PACMA 31 targets TrxR in cells to induce oxidative stress-mediated cancer cell apoptosis. Our results provide a new structural type of TrxR inhibitor that may serve as a useful probe for investigating the biology of TrxR-implicated pathways, and uncover a new target of PACMA 31 that contributes to it becoming a candidate for cancer treatment.