Tryptophan Suppresses FTH1-Driven Ferritinophagy, a Key Correlate of Prognosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options. Ferritinophagy, an autophagy-dependent process regulating iron metabolism, has emerged as a key contributor to ferroptosis and tumour progression. This study hypothesised that the ferritinophagy-related gene FTH1 drives HCC pathogenesis by modulating tryptophan metabolism and reactive oxygen species (ROS)-dependent ferroptosis.

Bayesian Optimization-Enhanced Reinforcement learning for Self-adaptive and multi-objective control of wastewater treatment.

Controllers of wastewater treatment plants (WWTPs) often struggle to maintain optimal performance due to dynamic influent characteristics and the need to balance multiple operational objectives. In this study, Reinforcement Learning (RL) algorithms across different activated sludge process configurations was tested, and a novel approach that integrates RL with Bayesian Optimization (BO) to enhance the control of critical operational parameters in activated sludge processes was developed. This study extended the application of advanced machine learning techniques to complex WWTP control problems, moving beyond simplified benchmarks.

Coordination Chemistry of Sulfur-Containing Bifunctional Chelators: Toward Stabilization of Cu PET Imaging Agents for Alzheimer's Disease.

The broader utilization of Cu positron emission tomography (PET) imaging agents has been hindered by the unproductive demetalation induced by bioreductants. To advance the development of Cu-based PET imaging tracers for Alzheimer's Disease (AD), there is a need for novel ligand design strategies. In this study, we developed sulfur-containing dithiapyridinophane (N2S2) bifunctional chelators (BFCs) as well as all nitrogen-based diazapyridinophane (N4) BFCs to compare their abilities to chelate Cu and target Aβ aggregates.

Amphiphilic Molecules Exhibiting Zwitterionic Excited-State Intramolecular Proton Transfer and Near-Infrared Emission for the Detection of Amyloid β Aggregates in Alzheimer's Disease.

Chromophores with zwitterionic excited-state intramolecular proton transfer (ESIPT) have been shown to have larger Stock shifts and red-shifted emission wavelengths compared to the conventional π-delocalized ESIPT molecules. However, there is still a dearth of design strategies to expand the current library of zwitterionic ESIPT compounds. Herein, a novel zwitterionic excited-state intramolecular proton transfer system is reported, enabled by addition of 1,4,7-triazacyclononane (TACN) fragments on a dicyanomethylene-4H-pyran (DCM) scaffold.

Simultaneous Fe/Fe imaging shows Fe over Fe enrichment in Alzheimer's disease mouse brain.

Visualizing redox-active metal ions, such as Fe and Fe ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe and Fe simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe or Fe, revealing a decreased Fe/Fe ratio during ferroptosis and an increased Fe/Fe ratio in Alzheimer's disease mouse brain.

Amphiphilic stilbene derivatives attenuate the neurotoxicity of soluble Aβ oligomers by controlling their interactions with cell membranes.

The misfolded proteins or polypeptides commonly observed in neurodegenerative diseases, including Alzheimer's disease (AD), are promising drug targets for developing therapeutic agents. To target the amyloid-β (Aβ) peptide plaques and oligomers, the hallmarks of AD, we have developed twelve amphiphilic small molecules with different hydrophobic and hydrophilic fragments. fluorescence binding assays demonstrate that these amphiphilic compounds show high binding affinity to both Aβ plaques and oligomers, and six of them exhibit selective binding toward Aβ oligomers.

Tracking the binding of multi-functional fluorescent tags for Alzheimer's disease using quantitative multiphoton microscopy.

A recent theranostic approach to address Alzheimer's disease (AD) utilizes multifunctional targets that both tag and negate the toxicity of AD biomarkers. These compounds, which emit fluorescence with both an activation and a spectral shift in the presence of Aβ, were previously characterized with traditional fluorescence imaging for binary characterization. However, these multifunctional compounds have broad and dynamic emission spectra that are dependent on factors such as the local environment, presence of Aβ deposits, etc.

A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing*.

Most photoacoustic (PA) imaging agents are based on the repurposing of existing fluorescent dye platforms that exhibit non-optimal properties for PA applications. Herein, we introduce PA-HD, a new dye scaffold optimized for PA probe development that features a 4.8-fold increase in sensitivity and a red-shift of the λ from 690 nm to 745 nm to enable ratiometric imaging.

NitroxylFluor: A Thiol-Based Fluorescent Probe for Live-Cell Imaging of Nitroxyl.

Detection of nitroxyl (HNO), the transient one-electron reduced form of nitric oxide, is a significant challenge owing to its high reactivity with biological thiols (with rate constants as high as 10 M s). To address this, we report a new thiol-based HNO-responsive trigger that can compete against reactive thiols for HNO. This process forms a common N-hydroxysulfenamide intermediate that cyclizes to release a masked fluorophore leading to fluorescence enhancement.