A Potent,Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation

Polycomb group (PcG) proteins are epigenetic regulators that facilitate both embryonic development and cancer progression. PcG proteins form Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 lysine 27 (H3K27me3), a histone mark recognized by the N-terminal chromodomain (ChD) of the CBX subunit of canonical PRC1. There are five PcG CBX paralogs in humans. CBX2 in particular is upregulated in a variety of cancers, particularly in advanced prostate cancers. Using CBX2 inhibitors to understand and target CBX2 in prostate cancer is highly desirable; however, high structural similarity among the CBX ChDs has been challenging for developing selective CBX ChD inhibitors. Here, we utilize selections of focused DNA encoded libraries (DELs) for the discovery of a selective CBX2 chromodomain probe, SW2_152F. SW2_152F binds to CBX2 ChD with a K_d of 80 nM and displays 24-1000-fold selectivity for CBX2 ChD over other CBX paralogs in vitro. SW2_152F is cell permeable, selectively inhibits CBX2 chromatin binding in cells, and blocks neuroendocrine differentiation of prostate cancer cell lines in response to androgen deprivation.     

Synthesis and Properties of New Cleavable Cationic Surfactants Containing Carbonate Groups

A novel series of cleavable alkyltrimethylammonium surfactants with different hydrocarbon chain lengths (C8–16) were synthesized. A carbonate break site inserted between the polar head and the hydrocarbon chain makes these compounds hydrolyzable. The reagents used are renewable, (bio)degradable, or reusable. The hydrolysis of these cleavable surfactants will lead to the generation of fatty alcohols and choline, which is an essential biological nutrient. The surface activities in aqueous solution of the synthesized carbonates fulfill the requirement of being good surfactants. In addition, the cleavable compounds containing n-decyl and n-dodecyl chains showed similar or higher antimicrobial activities when compared to a non-cleavable analog.     

Prenylated Flavonoids with Potential Antimicrobial Activity: Synthesis,Biological Activity,and In Silico Study

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7–13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 4′ are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.     

Effect of Exogenous Auxin Treatment on Cell Wall Polymers of Strawberry Fruit

The role of auxin in the fruit-ripening process during the early developmental stages of commercial strawberry fruits (Fragaria x ananassa) has been previously described, with auxin production occurring in achenes and moving to the receptacle. Additionally, fruit softening is a consequence of the depolymerization and solubilization of cell wall components produced by the action of a group of proteins and enzymes. The aim of this study was to compare the effect of exogenous auxin treatment on the physiological properties of the cell wall-associated polysaccharide contents of strawberry fruits. We combined thermogravimetric (TG) analysis with analyses of the mRNA abundance, enzymatic activity, and physiological characteristics related to the cell wall. The samples did not show a change in fruit firmness at 48 h post-treatment; by contrast, we showed changes in the cell wall stability based on TG and differential thermogravimetric (DTG) analysis curves. Less degradation of the cell wall polymers was observed after auxin treatment at 48 h post-treatment. The results of our study indicate that auxin treatment delays the cell wall disassembly process in strawberries.     

Astringency sub-qualities of red wines and the influence of wine–saliva aggregates

Astringency is a sensory attribute, related to the quality and mouthfeel of red wines. However, the origin of astringency sub-qualities, such as the typical drying astringency found in immature grapes, is still unknown. Astringency of red wines with similar tannin content but different astringency sub-qualities, from different harvest dates, is studied. Astringency was characterised in terms of friction coefficient, polyphenol content, sensory analysis and tannin/salivary–proteins aggregates characterisation. A different evolution during ripening was found for both Cabernet Sauvignon and Carménère, and tannin–protein aggregates showed differences in size, shape and surface. The velvety sub-quality appears to be related to aggregates with low precipitation, and with specific surface characteristics as roundness and Feret diameter. Results from this work propose an effect of aggregates on sensory perception and opens the possibility to explore their effect on oral lubrication.     

sInfluence of starch and protein molecular interactions on the in vitro digestion characteristics of biscuits partially substituted with pulse flours

Recent research has shown that pulse-derived ingredients present a technological alternative to cereals, higher protein and fibre content, and differentiated starch characteristics. In this work, the partial substitution of pulse flours with and without heat moisture treatment (HMT) was evaluated in a biscuit model. The digestion residues at 20 and 120 min that correspond to rapidly, slowly and resistant starch from the Englyst methodology were analysed by DSC, X-Ray and ATR-FTIR. The use of pulse flours in biscuits improved their thermal stability (ΔH = 3.01 and 4.99 J/g for control and Lentil + HMT), preserving a fraction of particularly ling glucans, that influenced the decreasing in the rapidly available starch from 55.26 to 24.11 % (Control and Faba bean + HMT), and enhanced its protein's digestibility from 75.26 to 87.43 % for the same sources. Among pulses, there were similarities regarding their resistance to enzymatic hydrolysis that may help select those with better organoleptic attributes.     

Wrapping up Metal–Organic Framework Crystals with Carbon Nanotubes

The presence of tetrazine units in the organic nodes of UiO-68-TZCD controls the formation of ultrathin coatings of single-wall nanotubes that decorate the surface of the crystal. These crystal hybrids can be prepared straightforwardly in one step and are extraordinarily respectful with the properties of the framework for combination of mesoporosity and surface areas ≈4.000 m² g⁻¹, with excellent stability in water, and conductivities at room temperature of 4 × 10⁻² S cm⁻¹ even at very low carbon weight contents (2.3 wt.%).