Developing Orthogonal Fluorescent RNAs for Photoactive Dual-Color Imaging of RNAs in Live Cells.

Fluorogenic RNA aptamers have revolutionized the visualization of RNAs within complex cellular processes. A representative category of them employs the derivatives of green fluorescent protein chromophore, 4-hydroxybenzlidene imidazolinone (HBI), as chromophores. However, the structural homogeneity of their chromophoric backbones causes severe cross-reactivity with other homologous chromophores.

Direct Visualization of Hepatitis C Virus RNA in Living Cells and Mice.

RNA virus infection is a global health issue with a significant economic burden. Direct visualization of the viral RNA genome in living cells is crucial for virological research and early clinical diagnosis. Thus, the need to continue research to find imaging toolkits is urgent.

CircUGP2 Suppresses Intrahepatic Cholangiocarcinoma Progression via p53 Signaling Through Interacting With PURB to Regulate ADGRB1 Transcription and Sponging miR-3191-5p.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients' prognosis.

Evaluation of WRF-Chem air quality forecasts during the AEROMMA and STAQS 2023 field campaigns.

A real-time air quality forecasting system was developed using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) to provide support for flight planning activities during the NOAA Atmospheric Emissions and Reactions Observed from Megacities to Marine Areas (AEROMMA) and NASA Synergistic TEMPO Air Quality Science (STAQS) 2023 field campaigns. The forecasting system operated on two separate domains centered on Chicago, IL, and New York City, NY, and provided 72-hour predictions of atmospheric composition, aerosols, and clouds. This study evaluates the Chicago-centered forecasting system's 1-, 2-, and 3-day ozone (O) forecast skill for Chiwaukee Prairie, WI, a rural area downwind of Chicago that often experiences high levels of O pollution.

A universal orthogonal imaging platform for living-cell RNA detection using fluorogenic RNA aptamers.

MicroRNAs (miRNAs) are crucial regulators of gene expression at the post-transcriptional level, offering valuable insights into disease mechanisms and prospects for targeted therapeutic interventions. Herein, we present a class of miRNA-induced light-up RNA sensors (miLS) that are founded on the toehold mediated principle and employ the fluorogenic RNA aptamers Pepper and Squash as imaging modules. By incorporating a sensor switch to disrupt the stabilizing stem of these aptamers, our design offers enhanced flexibility and convertibility for different target miRNAs and aptamers.

A Photolabile Curcumin-Diazirine Analogue Enables Phototherapy with Physically and Molecularly Produced Light for Alzheimer's Disease Treatment.

The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to explore non-traditional therapeutic avenues. In this study, we present the use of a photolabile curcumin-diazirine analogue, CRANAD-147, to induce changes in properties, structures (sequences), and neurotoxicity of amyloid beta (Aβ) species both in cells and in vivo.

Bioluminescence Imaging with Functional Amyloid Reservoirs in Alzheimer's Disease Models.

Bioluminescence imaging has changed the daily practice of preclinical research on cancer and other diseases over the last few decades; however, it has rarely been applied in preclinical research on Alzheimer's disease (AD). In this Article, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Aβ) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Aβ aggregates and plaques.

Engineering fluorescent protein chromophores with an internal reference for high-fidelity ratiometric G4 imaging in living cells.

G-quadruplexes (G4s) are significant nucleic acid secondary structures formed by guanine-rich sequences. Many single-emission G4 fluorescent probes that are lit up by inhibiting intramolecular rotation have been reported. However, they are non-fluorescent unless structurally rigidified, making them sensitive to other intracellular crowding and confinement environments in the cell, like viscosity.

Advances in G-quadruplexes-based fluorescent imaging.

G-quadruplexes (G4s), the noncanonical nucleic acid secondary structure, form within guanine-rich DNA or RNA sequences. G4s formation can affect chromatin architecture and gene regulation and has been associated with various cellular functions, including DNA replication, transcription, and genome maintenance. Visualizing and detecting G4s precisely in such processes is essential to increasing our understanding of G4s biology.

Multifunctional stimuli-responsive chemogenetic platform for conditional multicolor cell-selective labeling.

Multicolor conditional labeling is a powerful tool that can simultaneously and selectively visualize multiple targets for bioimaging analysis of complex biological processes and cellular features. We herein report a multifunctional stimuli-responsive Fluorescence-Activating and absorption-Shifting Tag (srFAST) chemogenetic platform for multicolor cell-selective labeling. This platform comprises stimuli-responsive fluorogenic ligands and the organelle-localizable FAST.

Visualization of Deep Tissue G-quadruplexes with a Novel Large Stokes-Shifted Red Fluorescent Benzothiazole Derivative.

G-quadruplex (G4) is a noncanonical nucleic acid secondary structure that has implications for various physiological and pathological processes and is thus essential to exploring new approaches to G4 detection in live cells. However, the deficiency of molecular imaging tools makes it challenging to visualize the G4 in ex vivo tissue samples. In this study, we established a G4 probe design strategy and presented a red fluorescent benzothiazole derivative, , to detect and image G4 structures in living cells and tissue samples.

Photodecaging of a Mitochondria-Localized Iridium(III) Endoperoxide Complex for Two-Photon Photoactivated Therapy under Hypoxia.

Despite the clinical success of photodynamic therapy (PDT), the application of this medical technique is intrinsically limited by the low oxygen concentrations found in cancer tumors, hampering the production of therapeutically necessary singlet oxygen (O). To overcome this limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (), which, upon two-photon irradiation in NIR, synergistically releases a highly cytotoxic iridium(III) complex (), singlet oxygen, and an alkoxy radical. was found to be highly (photo-)toxic in hypoxic tumor cells and multicellular tumor spheroids (MCTS) in the nanomolar range.

A mitochondrion-targeted BODIPY-Ir(III) conjugate as a photoinduced ROS generator for the oxidative destruction of triple-negative breast cancer cells.

Photodynamic therapy (PDT) provides an alternative option to root out localized triple-negative breast cancer (TNBC) and has been experiencing a surge of research interest over recent years. In this study, we put forward a paradigm of designing novel transition metal-based PSs with the following characteristics: favorable cell-permeability, significant light-harvesting ability and prominent ROS yield. A novel BODIPY-Ir(III) conjugate has been designed as a photoinduced ROS (O, ˙OH and ˙O) generator.

Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging.

Objectives: To enable non-invasive real-time quantification of vasopressin 1A (V1A) receptors in peripheral organs, we sought to develop a suitable PET probe that would allow specific and selective V1A receptor imaging in vitro and in vivo.

Methods: We synthesized a high-affinity and -selectivity ligand, designated compound 17. The target structure was labeled with carbon-11 and tested for its utility as a V1A-targeted PET tracer by cell uptake studies, autoradiography, in vivo PET imaging and ex vivo biodistribution experiments.

Ruthenium(II) complexes coordinated to graphitic carbon nitride: Oxygen self-sufficient photosensitizers which produce multiple ROS for photodynamic therapy in hypoxia.

The photodynamic therapy (PDT) of cancer is limited by tumor hypoxia as PDT efficiency depends on O concentration. A novel oxygen self-sufficient photosensitizer (Ru-g-CN) was therefore designed and synthesized via a facile one-pot method in order to overcome tumor hypoxia-induced PDT resistance. The photosensitizer is based on [Ru(bpy)] coordinated to g-CN nanosheets by Ru-N bonding.

β-Amyloid Peptides Manipulate Switching Behaviors of Donor-Acceptor Stenhouse Adducts.

Molecular switching plays a critical role in biological and displaying systems. Donor-acceptor Stenhouse adducts (DASAs) is a newly re-discovered series of switchable photochromes, and light is the most used approach to control its switching behavior. In this report, we speculated that hydrophobic binding pockets of biologically relevant peptides/proteins could be harnessed to alter its switching behavior without the assistance of light.

Nano-assembly of ruthenium(II) photosensitizers for endogenous glutathione depletion and enhanced two-photon photodynamic therapy.

Photodynamic therapy (PDT) is a promising noninvasive cancer treatment. PDT in the clinic faces several hurdles due to the unique tumor environment, a feature of which is high levels of glutathione (GSH). An excess amount of GSH consumes reactive oxygen species (ROS) generated by photosensitizers (PSs), reducing PDT efficiency.

A Mitochondrion-Localized Two-Photon Photosensitizer Generating Carbon Radicals Against Hypoxic Tumors.

The efficacy of photodynamic therapy is typically reliant on the local concentration and diffusion of oxygen. Due to the hypoxic microenvironment found in solid tumors, oxygen-independent photosensitizers are in great demand for cancer therapy. We herein report an iridium(III) anthraquinone complex as a mitochondrion-localized carbon-radical initiator.

One- and Two-Photon Phototherapeutic Effects of Ru Polypyridine Complexes in the Hypoxic Centre of Large Multicellular Tumor Spheroids and Tumor-Bearing Mice*.

During the last decades, photodynamic therapy (PDT), an approved medical technique, has received increasing attention to treat certain types of cancer. Despite recent improvements, the treatment of large tumors remains a major clinical challenge due to the low ability of the photosensitizer (PS) to penetrate a 3D cellular architecture and the low oxygen concentrations present in the tumor center. To mimic the conditions found in clinical tumors, exceptionally large 3D multicellular tumor spheroids (MCTSs) with a diameter of 800 μm were used in this work to test a series of new Ru polypyridine complexes as one-photon and two-photon PSs.

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy.

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum.

Boosting two-photon photodynamic therapy with mitochondria-targeting ruthenium-glucose conjugates.

Herein, we present a series of dual-targeted ruthenium-glucose conjugates that can function as two-photon absorption (TPA) PDT agents to effectively destroy tumors by preferentially targeting both tumor cells and mitochondria. The in vivo experiments revealed an excellent tumor inhibitory efficiency of the dual-targeted TPA PSs.

FerriIridium: A Lysosome-Targeting Iron(III)-Activated Iridium(III) Prodrug for Chemotherapy in Gastric Cancer Cells.

Reported is the Fe -activated lysosome-targeting prodrug FerriIridium for gastric cancer theranostics. It contains a meta-imino catechol group that can selectively bond to, and be oxidized by, free Fe inside the cell. Subsequent oxidative rearrangement releases Fe and hydrolyses the amine bond under acidic conditions, forming an aminobipyridyl Ir complex and 2-hydroxybenzoquinone.

Ozone Variability and Anomalies Observed during SENEX and SEACRS Campaigns in 2013.

Tropospheric ozone variability occurs because of multiple forcing factors including surface emission of ozone precursors, stratosphere-to-troposphere transport (STT), and meteorological conditions. Analyses of ozonesonde observations made in Huntsville, AL, during the peak ozone season (May to September) in 2013 indicate that ozone in the planetary boundary layer was significantly lower than the climatological average, especially in July and August when the Southeastern United States (SEUS) experienced unusually cool and wet weather. Because of a large influence of the lower stratosphere, however, upper-tropospheric ozone was mostly higher than climatology, especially from May to July.

Quantifying TOLNet Ozone Lidar Accuracy during the 2014 DISCOVER-AQ and FRAPPÉ Campaigns.

The Tropospheric Ozone Lidar Network (TOLNet) is a unique network of lidar systems that measure high-resolution atmospheric profiles of ozone. The accurate characterization of these lidars is necessary to determine the uniformity of cross-instrument calibration. From July to August 2014, three lidars, the TROPospheric OZone (TROPOZ) lidar, the Tunable Optical Profiler for Aerosol and oZone (TOPAZ) lidar, and the Langley Mobile Ozone Lidar (LMOL), of TOLNet participated in the "Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality" (DISCOVER-AQ)mission and the "Front Range Air Pollution and Photochemistry Éxperiment" (FRAPPÉ)to measure ozone variations from the boundary layer to the top of the troposphere.

Langley mobile ozone lidar: ozone and aerosol atmospheric profiling for air quality research.

The Langley mobile ozone lidar (LMOL) is a mobile ground-based ozone lidar system that consists of a pulsed UV laser producing two UV wavelengths of 286 and 291 nm with energy of approximately 0.2  mJ/pulse and repetition rate of 1 kHz. The 527 nm pump laser is also transmitted for aerosol measurements.