Knockdown of 14-3-3ζ enhances radiosensitivity and radio-induced apoptosis in CD133+ liver cancer stem cells

14-3-3ζ is related to many cancer survival cellular processes. In a previous study, we showed that silencing 14-3-3ζ decreases the resistance of hepatocellular carcinoma (HCC) to chemotherapy. In this study, we investigated whether silencing 14-3-3ζ affects the radioresistance of cancer stem-like cells (CSCs) in HCC. Knockdown of 14-3-3ζ decreased cell viability and the number of spheres by reducing radioresistance in CSCs after γ-irradiation (IR). Furthermore, the levels of pro-apoptotic proteins were upregulated in CSCs via silencing 14-3-3ζ after IR. These results suggest that 14-3-3ζ knockdown enhances radio-induced apoptosis by reducing radioresistance in liver CSCs.     

Visible‐Light Sensitization of Vinyl Azides by Transition‐Metal Photocatalysis

Irradiation of vinyl and aryl azides with visible light in the presence of Ru photocatalysts results in the formation of reactive nitrenes, which can undergo a variety of C? N bond‐forming reactions. The ability to use low‐energy visible light instead of UV in the photochemical activation of azides avoids competitive photodecomposition processes that have long been a significant limitation on the synthetic use of these reactions.     

Simultaneous In Situ Quantification of Two Cellular Lipid Pools Using Orthogonal Fluorescent Sensors

Lipids regulate a wide range of biological activities. Since their local concentrations are tightly controlled in a spatiotemporally specific manner, the simultaneous quantification of multiple lipids is essential for elucidation of the complex mechanisms of biological regulation. Here, we report a new method for the simultaneous in situ quantification of two lipid pools in mammalian cells using orthogonal fluorescent sensors. The sensors were prepared by incorporating two environmentally sensitive fluorophores with minimal spectral overlap separately into engineered lipid‐binding proteins. Dual ratiometric analysis of imaging data allowed accurate, spatiotemporally resolved quantification of two different lipids on the same leaflet of the plasma membrane or a single lipid on two opposite leaflets of the plasma membrane of live mammalian cells. This new imaging technology should serve as a powerful tool for systems‐level investigation of lipid‐mediated cell signaling and regulation.     

Mechanical Force Induces Ylide-Free Cycloaddition of Nonscissible Aziridines

The application of aziridines as nonvulnerable mechanophores is reported. Upon exposure to a mechanical force, stereochemically pure nonactivated aziridines incorporated into the backbone of a macromolecule do not undergo cis–trans isomerization, thus suggesting retention of the ring structure under force. Nonetheless, aziridines react with a dipolarophile and seem not to obey conventional reaction pathways that involve C−C or C−N bond cleavage prior to the cycloaddition. Our work demonstrates that a nonvulnerable chemical structure can be a mechanophore.     

An Activatable AIEgen Probe for High‐Fidelity Monitoring of Overexpressed Tumor Enzyme Activity and Its Application to Surgical Tumor Excision

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM‐ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline‐malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP‐recognition units. The rapid liberation of DQM‐OH aggregates in the presence of ALP resulted in aggregation‐induced fluorescence. The up‐regulation of ALP expression in tumor cells was imaged using DQM‐ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two‐photon microscopy platform, providing the fluorescence‐guided recognition of sub‐millimeter tumorigenesis. DQM‐ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.     

Nanocatalosomes as Plasmonic Bilayer Shells with Interlayer Catalytic Nanospaces for Solar‐Light‐Induced Reactions

Interest and challenges remain in designing and synthesizing catalysts with nature‐like complexity at few‐nm scale to harness unprecedented functionalities by using sustainable solar light. We introduce “nanocatalosomes”—a bio‐inspired bilayer‐vesicular design of nanoreactor with metallic bilayer shell‐in‐shell structure, having numerous controllable confined cavities within few‐nm interlayer space, customizable with different noble metals. The intershell‐confined plasmonically coupled hot‐nanospaces within the few‐nm cavities play a pivotal role in harnessing catalytic effects for various organic transformations, as demonstrated by “acceptorless dehydrogenation”, “Suzuki–Miyaura cross‐coupling” and “alkynyl annulation” affording clean conversions and turnover frequencies (TOFs) at least one order of magnitude higher than state‐of‐the‐art Au‐nanorod‐based plasmonic catalysts. This work paves the way towards next‐generation nanoreactors for chemical transformations with solar energy.     

A Sensor for Serotonin and Dopamine Detection in Cancer Cells Line Based on the Conducting Polymer−Pd Complex Composite

An electrochemical sensor based on the conducting polymer composite with a palladium complex (Pd(C₂H₄N₂S₂)₂) was developed for the detection of serotonin and dopamine simultaneously in the breast cancer cell and human plasma samples. The proposed sensor was fabricated using the Pd(C₂H₄N₂S₂)₂ complex‐anchored poly2,2 : 5,2‐terthiophene‐3‐(p‐benzoic acid) (pTBA) layer on the AuNPs decorated reduced graphene oxide (AuNPs@rGO) substrate, which revealed the enhanced anodic current of the target species. The sensor probe was characterized by electrochemical and surface analysis methods. The experimental parameters affecting the sensor performance were optimized, in terms of AuNPs@rGO concentration, the number of electropolymerization cycle for pTBA, immobilization time of Pd(C₂H₄N₂S₂)₂, and pH. The dynamic ranges for serotonin and dopamine were obtained from 0.02 to 200 μM, and from 0.1 to 200 μM with the detection limit of 2.5, and 24.0 nM, respectively. The reliability of proposed sensor was evaluated using cancer cell lines for the clinical applications.     

Synthesis and Structure–Activity Relationship Studies of Benzimidazole-4,7-dione-Based P2X3 Receptor Antagonists as Novel Anti-Nociceptive Agents

P2X3 receptors (P2X3R) are ATP-gated ion channels predominantly expressed in C- and Aδ-fiber primary afferent neurons and have been introduced as a novel therapeutic target for neurological disorders, including neuropathic pain and chronic cough. Because of its localized distribution, antagonism of P2X3R has been thoroughly considered, and the avoidance of issues related to CNS side effects has been proven in clinical trials. In this article, benzimidazole-4,7-dione-based derivatives were introduced as a new chemical entity for the development of P2X3R antagonists. Starting from the discovery of a hit compound from the screening of 8364 random library compounds in the Korea Chemical Bank, which had an IC₅₀ value of 1030 nM, studies of structure–activity and structure–property relationships enabled further optimization toward improving the antagonistic activities as well as the drug’s physicochemical properties, including metabolic stability. As for the results, the final optimized compound 14h was developed with an IC₅₀ value of 375 nM at P2X3R with more than 23-fold selectivity versus P2X2/3R, along with properties of metabolic stability and improved solubility. In neuropathic pain animal models evoked by either nerve ligation or chemotherapeutics in male Sprague-Dawley rats, compound 14h showed anti-nociceptive effects through an increase in the mechanical withdrawal threshold as measured by von Frey filament following intravenous administration.     

Growth of 2-methyl-4-nitroaniline (MNA) crystals by the bridgman method

Organic single crystals of 2-methyl-4-nitroaniline (MNA) up to 3 mm in diameter and 20 mm in length have been successfully grown by the Bridgman method using the purified reagent by sublimation. The crystals are transparent and yellow in colour by controlling the growth conditions. In the spectra of yellow coloured crystals no absorption peak is observed until about 450 nm. Also, the crystals of MNA have the two cleavage planes (311 ) and (010).