Coenzyme Q0 defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells.

Coenzyme Q0 (CoQ0) is a derivative quinone from Antrodia camphorata (AC) that exerts anticancer activities. This study examined the anticancer attributes of CoQ0 (0-4 µM) on inhibited anti-EMT/metastasis and NLRP3 inflammasome, and altered Warburg effects via HIF-1α inhibition in triple-negative breast cancer (MDA-MB-231 and 468) cells. MTT assay, cell migration/invasion assays, Western blotting, immunofluorescence, metabolic reprogramming, and LC-ESI-MS were carried out to assess the therapy potential of CoQ0. CoQ0 inhibited HIF-1α expression and suppressed the NLRP3 inflammasome and ASC/caspase-1 expression, followed by downregulation of IL-1ß and IL-18 expression in MDA-MB-231 and 468 cells. CoQ0 ameliorated cancer stem-like markers by decreasing CD44 and increasing CD24 expression. Notably, CoQ0 modulated EMT by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal marker N-cadherin. CoQ0 inhibited glucose uptake and lactate accumulation. CoQ0 also inhibited HIF-1α downstream genes involved in glycolysis, such as HK-2, LDH-A, PDK-1, and PKM-2 enzymes. CoQ0 decreased extracellular acidification rate (ECAR), glycolysis, glycolytic capacity, and glycolytic reserve in MDA-MB-231 and 468 cells under normoxic and hypoxic (CoCl2) conditions. CoQ0 inhibited the glycolytic intermediates lactate, FBP, and 2/3-PG, and PEP levels. CoQ0 increased oxygen consumption rate (OCR), basal respiration, ATP production, maximal respiration, and spare capacity under normoxic and hypoxic (CoCl2) conditions. CoQ0 increased TCA cycle metabolites, such as citrate, isocitrate, and succinate. CoQ0 inhibited aerobic glycolysis and enhanced mitochondrial oxidative phosphorylation in TNBC cells. Under hypoxic conditions, CoQ0 also mitigated HIF-1α, GLUT1, glycolytic-related (HK-2, LDH-A, and PFK-1), and metastasis-related (E-cadherin, N-cadherin, and MMP-9) protein or mRNA expression in MDA-MB-231 and/or 468 cells. Under LPS/ATP stimulation, CoQ0 inhibited NLRP3 inflammasome/procaspase-1/IL-18 activation and NFκB/iNOS expression. CoQ0 also hindered LPS/ATP-stimulated tumor migration and downregulated LPS/ATP-stimulated N-cadherin and MMP-2/-9 expression. The present study revealed that suppression of HIF-1α expression caused by CoQ0 may contribute to inhibition of NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects of triple-negative breast cancers.

Photochemical Radical Bicyclization of 1,5-Enynes: Divergent Synthesis of Fluorenes and Azepinones.

A dual nickel- and iridium-photocatalyzed radical cascade bicyclization reaction for the synthesis of highly complex molecular structures in an atom- and step-economic manner has been described. A series of radical precursors are utilized for the divergent synthesis of diversely substituted fluorenes and indenoazepinones bearing quaternary carbons by using cascade cyclization reactions of 1,5-enynes. This reaction is characterized by its mild conditions, broad substrate scope, excellent selectivity, and satisfactory yield including facile scale-up synthesis.

Ferroelectricity and Oxide Reliability of Stacked Hafnium-Zirconium Oxide Devices.

In this work, we investigate the ferroelectricity of stacked zirconium oxide and hafnium oxide (stacked HfZrO) with different thickness ratios under metal gate stress and simultaneously evaluate the electrical reliability of stacked ferroelectric films. Based on experimental results, we find that the stacked HfZrO films not only exhibited excellent ferroelectricity but also demonstrated a high performance on reliability. The optimized condition of the 45% Zr proportion exhibited a robust ferroelectric polarization value of 32.57 µC/cm2, and a polarization current with a peak value of 159.98 µA. Besides this, the ferroelectric stacked HfZrO also demonstrated good reliability with a ten-year lifetime under >-2 V constant voltage stress. Therefore, the appropriate modulation of zirconium proportion in stacked HfZrO showed great promise for integrating in high-performance ferroelectric memory.

Study of release speeds and bacteria inhibiting capabilities of drug delivery membranes fabricated via electrospinning by observing bacteria growth curves.

The study found that biodegradable drug delivery membranes that were fabricated from Poly(a-L-alanine) (PLLA) and chlorhexidine (CHX)-gluconate via electrospinning could steadily and continuously inhibit the growth of bacteria. Bacterial growth curves were used to evaluate on a real-time basis the relationship between drug delivery speeds of the membranes and growth rates of bacteria in different phases. The results showed that PLLA/CHX (50:50 in terms of volume) drug delivery membranes could do what drug delivery systems can normally do. SEM morphology observations, FTIR, and Raman spectra analyses were conducted on the drug delivery membranes. This is the first study that confirms that biodegradable CHX delivery membranes fabricated via electrospinning are a rate-preprogrammed drug delivery system by comparing the growth curves of competent cell and plasmid inserted competent cell, bacteria that are of the same strain but grow at different speeds due to the insertion.

Enhanced thermoelectricity of three-dimensionally mesostructured BixSb2-xTe3 nanoassemblies: from micro-scaled open gaps to isolated sealed mesopores.

We describe an innovative interfacial design concept and nanostructuring of novel BixSb2-xTe3 (BST) nanoassembled films comprising unique air-solid interfaces from micro-scaled open gaps to isolated sealed mesopores, and high-quality solid-solid ones including the coherent grain boundaries and specific twins, utilizing pulsed laser deposition (PLD), for potentially activating multiple thermoelectric enhancing mechanisms. The unusual mesopore embedded BST films exhibit the highest power factor of ∼33 µW cm-1 K-2, which is comparable to or higher than the previously reported values for BST, and the corresponding relatively low thermal diffusivity in contrast to that for dense pore-less BST films evidently reveals the crucial role of the three-dimensionally and densely arranged air-solid interfaces in significantly arising the phonon scattering.

Dihydrobenzoic acid modified nanoparticle as a MALDI-TOF MS matrix for soft ionization and structure determination of small molecules with diverse structures.

Efficient structural characterization is important for quality control when developing novel materials. In this study, we demonstrated the soft ionization capability of the hybrid of immobilized silica and 2,5-dihydrobenzoic acid (DHB) on iron oxide magnetic nanoparticles in MALDI-TOF MS with a clean background. The ratio between SiO(2) and DHB was examined and was found to affect the surface immobilization of DHB on the nanoparticle, critically controlling the ionization efficiency and interference background. Compared with commercial DHB, the functionalized nanoparticle-assisted MALDI-TOF MS provided superior soft ionization with production of strong molecular ions within 5 ppm mass accuracy on a variety of new types of synthetic materials used for solar cells, light emitting devices, dendrimers, and glycolipids, including analytes with either thermally labile structures or poor protonation tendencies. In addition, the enhancements of the molecular ion signal also provided high-quality product-ion spectra allowing structural characterization and unambiguous small molecule identification. Using this technique, the structural differences among the isomers were distinguished through their characteristic fragment ions and comprehensive fragmentation patterns. With the advantages of long-term stability and simple sample preparation by deposition on a regular sample plate, the use of DHB-functionalized nanoparticles combined with high-resolution MALDI-TOF MS provides a generic platform for rapid and unambiguous structure determination of small molecules.

Synthesis of alpha-(2-->5)Neu5Gc oligomers.

A facile synthesis of the sialic acid oligomers alpha-(2-->5)Neu5Gc (1) is presented. Monosaccharides 2-4 with suitable functionality were used as the building blocks. After selective removal of the paired carboxyl and amine protecting groups, the fully protected oligomers were assembled through consecutive coupling of the building blocks by well established peptide coupling techniques. By this approach, fully protected oligomers as large as an octasaccharide were synthesized. Deprotection of these fully protected oligomers was conducted in two steps (LiCl in refluxing pyridine and 0.1 n NaOH) to afford the desired products in high yield. Enzymatic degradation of the octamer with neuraminidase, monitored by capillary electrophoresis (CE), was also accomplished. The stepwise exo-cleavage adducts were all well separated and identified in the CE spectrum. The strategy described here for solution-phase synthesis also provides the basis for future solid-phase synthesis of poly-alpha-(2-->5)Neu5Gc.