Selective detection of mitochondrial Cu in living cells by a near-infrared iridium(III) complex.

The widespread use of copper (Cu) has raised concerns about environmental pollution and adverse effects on human health, highlighting the need to develop copper detection methods. Developing near-infrared (NIR) luminescent probes for imaging subcellular Cu is still a challenge. In this work, we have developed a luminescence probe based on a NIR iridium(III) complex, which rapidly detects Cu by combining salicylaldehyde and amine groups through a simple Schiff base reaction on the N^N ligand.

An iridium(III) complex-based luminogenic probe for high-throughput screening of hydrogen sulfide donors in living cells.

The scarcity of suitable high-throughput screening technology for hydrogen sulfide (HS) donors has hampered the discovery of HS donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted HS probe to monitor the real-time dynamic change of HS. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor HS in living cells with decreased false negative results.

Tailoring obeticholic acid activity by iridium(III) complex conjugation to develop a farnesoid X receptor probe.

Introduction: The farnesoid X receptor (FXR) is a crucial regulator in the intestine, maintaining bile acid homeostasis. Inhibiting intestinal FXR shows promise in managing inflammatory bowel and liver diseases by reducing bile acid accumulation. Additionally, changes in FXR expression could serve as a potential biomarker for intestinal diseases.

Development of a NIR Iridium(III) Complex-Based Probe for the Selective Detection of Iron(II) Ions.

As a commonly used metal ion, iron(II) (Fe) ions pose a potential threat to ecosystems and human health. Therefore, it is particularly important to develop analytical techniques for the rapid and accurate detection of Fe ions. However, the development of near-infrared (NIR) luminescence probes with good photostability for Fe ions remain challenging.

KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges.

Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations in the rates of progression-free disease and overall survival of patients.

Repurposing sodium stibogluconate as an uracil DNA glycosylase inhibitor against prostate cancer using a time-resolved oligonucleotide-based drug screening platform.

Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention.

Recent discoveries of the role of histone modifications and related inhibitors in pathological cardiac hypertrophy.

Pathological cardiac hypertrophy is a common response of the heart to various pathological stimuli. In recent years, various histone modifications, including acetylation, methylation, phosphorylation and ubiquitination, have been identified to have crucial roles in regulating chromatin remodeling and cardiac hypertrophy. Novel drugs targeting these epigenetic changes have emerged as potential treatments for pathological cardiac hypertrophy.

Covalent inhibition of epidermal growth factor receptor using a long-lived iridium(III)-afatinib probe.

The overexpression and overactivation of epidermal growth factor receptor (EGFR) are frequently observed in human cancers, including squamous cell carcinoma and adenocarcinoma. In this study, a covalent EGFR probe was developed by conjugating afatinib to an iridium(III) scaffold. Complex 1 showed enhanced luminescence in living epidermoid squamous carcinoma A431 cells compared to other cell lines, via engaging EGFR as confirmed via CETSA and knockdown experiments.

A glycyrrhetinic acid-iridium(III) conjugate as a theranostic NIR probe for hepatocellular carcinoma with mitochondrial-targeting ability.

Hepatocellular carcinoma (HCC) is a major contributor to global mortality rates, but current treatment options have limitations. Advanced theranostics are needed to effectively integrate diagnosis and therapeutic of HCC. Glycyrrhetinic acid (GA) has abundant binding sites with glycyrrhetinic acid receptors (GA-Rs) on the surface of HCC cells and has also been reported to possess ligands with mitochondrial-targeting capability but with limited efficacy.

A Switch-On Affinity-Based Iridium(III) Conjugate Probe for Imaging Mitochondrial Glutathione -Transferase in Breast Cancer Cells.

Glutathione -transferase is heterogeneously expressed in breast cancer cells and is therefore emerging as a potential diagnostic biomarker for studying the heterogeneity of breast cancers. However, available fluorescent probes for GSTs depend heavily on GSTs-catalyzed glutathione (GSH) nucleophilic substitution reactions, making them susceptible to interference by the high concentration of nucleophilic species in the cellular environment. Moreover, the functions of subcellular GSTs are generally overlooked due to the lack of suitable luminescence probes.

Exosomal miRNA-mediated intercellular communications and immunomodulatory effects in tumor microenvironments.

Extracellular communication, in other words, crosstalk between cells, has a pivotal role in the survival of an organism. This communication occurs by different methods, one of which is extracellular vesicles. Exosomes, which are small lipid extracellular vesicles, have recently been discovered to have a role in signal transduction between cells inside the body.

Highly Active Single-Atom Nanozymes with High-Loading Iridium for Sensitive Detection of Pesticides.

Single-atom nanozymes (SAzymes) are novel mimic-enzyme materials with atomically doped active sites. They play a pivotal role in the field of nanozymes because of their excellent catalytic activities, high utilization efficiency of the metal atoms, and simple model of active sites. Herein, the peroxidase (POD)-like SAzymes with high-loading iridium (Ir) (5.

A cell-impermeable luminogenic probe for near-infrared imaging of prostate-specific membrane antigen in prostate cancer microenvironments.

Prostate-specific membrane antigen (PSMA) imaging probes are a promising tool for the diagnosis and image-guided surgery of prostate cancer (PCa). However, PSMA-specific luminescence probes for PCa detection and heterogeneity studies with high imaging contrast are lacking. Here, we report the first near-infrared (NIR) iridium(III) complex for the wash-free and specific imaging of PSMA in PCa cells and spheroids.

A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance.

Temozolomide (TMZ) is an anticancer agent used to treat glioblastoma, typically following radiation therapy and/or surgical resection. However, despite its effectiveness, at least 50% of patients do not respond to TMZ, which is associated with repair and/or tolerance of TMZ-induced DNA lesions. Studies have demonstrated that alkyladenine DNA glycosylase (AAG), an enzyme that triggers the base excision repair (BER) pathway by excising TMZ-induced N3-methyladenine (3meA) and N7-methylguanine lesions, is overexpressed in glioblastoma tissues compared to normal tissues.

Synthesis and luminescence monitoring of iridium(III) complex-functionalized gold nanoparticles and their application for determination of gold(III) ions.

A new method is presented for the one-step synthesis and real-time monitoring of iridium(III) complex-functionalized AuNPs from the precursor gold(III) chloride (AuCl). The functionalized AuNPs with an average size of 8 - 20 nm were obtained by the reduction of Au ions by the alkyne group of iridium(III) complexes, which was accompanied by the anchoring iridium(III) complexes on the surface of the nanoparticles. Meanwhile, the luminescence of the iridium(III) complexes was effectively quenched due to distance-dependent fluorescence quenching by AuNPs, thereby enabling luminescence monitoring of the formation process of the functionalized AuNPs and obtaining scattering information and spectral information in real time.

The role and prospect of lysine-specific demethylases in cancer chemoresistance.

Histone methylation plays a key function in modulating gene expression, and preserving genome integrity and epigenetic inheritance. However, aberrations of histone methylation are commonly observed in human diseases, especially cancer. Lysine methylation mediated by histone methyltransferases can be reversed by lysine demethylases (KDMs), which remove methyl marks from histone lysine residues.

Dehydroeburicoic Acid, a Dual Inhibitor against Oxidative Stress in Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a complicated disease which can lead to hepatocellular carcinoma; however, there is a lack of satisfactory therapeutics. Dehydroeburicoic acid (DEA) (), a triterpenoid isolated from , has been reported to act against ALD, but its mechanisms of action are still not clear. In this study, we report for the first time the use of DEA () as a dual inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) and GSK3β in an in vitro ALD cell model.

Imaging mitochondrial palladium species in living cells with a NIR iridium(III) complex.

The wide use of palladium (Pd) raises the concern about environmental pollution and human diseases, evoking the need for the development of detection methods for Pd species. However, the development of near-infrared (NIR) luminescence probes for subcellular Pd species remains challenging. In this work, we presented a NIR iridium(III) complex-based luminescence probe for the detection of Pd species through incorporating an allyl group and amino group into the N^N ligand.

Interference reduction isothermal nucleic acid amplification strategy for COVID-19 variant detection.

Common reference methods for COVID-19 variant diagnosis include viral sequencing and PCR-based methods. However, sequencing is tedious, expensive, and time-consuming, while PCR-based methods have high risk of insensitive detection in variant-prone regions and are susceptible to potential background signal interference in biological samples. Here, we report a loop-mediated interference reduction isothermal nucleic acid amplification (LM-IR-INA) strategy for highly sensitive single-base mutation detection in viral variants.