Amphoteric phosphocholine as a family of mild surfactants are widely used in biology due to their phosphate structure related to naturally occurring membrane lipids. Changing its hydrophobic part to the fluorocarbon counterparts, it was found that the interfacial properties of phosphocholine surfactants exhibit significant differences. Currently, the research on fluorinated phosphocholine surfactants is limited and lacks types of fluorinated hydrophobic structures. We found that oxygen atoms exhibit specificity in fluorinated surfactants in our previous works. In this work, a kind of phosphocholine containing a fluoroether hydrophobic chain was synthesized, and its interfacial properties, foam properties, and wetting properties were studied. At the beginning, we conducted a substitution reaction using fluoroether alcohols and 2-chloro-2-oxo-1,3,2-dioxaphospholane as raw materials, triethylamine as a base, and tetrahydrofuran (THF) as a solvent under ice bath. Then, the intermediate C72-P is obtained through distillation, which is a transparent viscous liquid with a yield of 70%. The next step is to dissolve the C72-P with trimethylamine (2 mol/L in THF) in acetonitrile at 70 degrees C for 48 h. Finally, a fluoroether phosphocholine surfactant was obtained and purified through column chromatography to give C72-MPB in 90% yield. Under the same conditions, a fluorinated linear phosphocholine surfactant 6:2-MPB was prepared using perfluorohexyl ethanol, which is a white solid with a overall yield of 60%. The phosphocholine fluorinated surfactants C72-MPB and 6: 2-MPB were diluted with distilled water to obtain various concentrations of solutions, the surface properties were measured by surface tension instrument Kruss K100C, and the surface tension was measured by Wilhelmy platinum plate method. On the other hand, the performance of foam under two different concentrations of C72-MPB was tested by bubbling method, and the morphology of foam was observed. C72-MPB solution was dropped onto the surface of polytetrafluoroethylene (PTFE), contact angle on PTFE was measured, and its wettability at different time was recorded. The results show that the new fluoroether phosphocholine surfactant has good solubility, low surface tension, good wettability, good foam stability. Fluoroether phosphocholine surfactants have potential utility value in the field of life sciences and medicine. It is a kind of surfactant with excellent application prospects.

2-Amino-5-nitro-4-(tetrazol-5-yl)-1,2,3-triazole (HANTT), its corresponding energetic salts and a dimeric azo compound are successfully synthesized. Compared to 5-nitro-4-(tetrazol-5-yl)-1,2,3-triazole (H2NTT), the neutral N-amino compound HANTT exhibits excellent properties in many aspects, including a higher density (rho = 1.86 g cm(-3)), a better detonation performance (D-v = 8931 m s(-1), P = 32.2 GPa) and a higher thermal decomposition temperature (T-d = 237 degree celsius). Among the prepared materials, the hydroxylammonium energetic salt exhibits the best detonation performance (D-v = 9096 m s(-1), P = 32.8 GPa) and an acceptable mechanical sensitivity (IS = 12 J, FS = 144 N). HANTT, the energetic salts and the azo compound are fully characterized by infrared spectroscopy, multinuclear NMR spectroscopy, elemental analysis and differential scanning calorimetry.

Cyclic annulation involving diaryliodonium salts is an efficient tool for the construction of two or more chemical bonds in a one -pot process. Ortho-functionalized diaryliodonium salts have showcased distinct reactivity in the exploration of benzocyclization or arylocyclization. With this strategy of ortho-ester-substituted diaryliodonium salts, herein, we utilized a copper catalyst to activate the C-I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents.

Son of sevenless homolog 1 (SOS1) plays a pivotal role as a molecular switch in the conversion of GDP -bound inactive KRAS to its active GTP-bound form, making SOS1 a promising therapeutic target for KRAS-driven cancers. While the most advanced SOS1 inhibitor has processed to phase I clinical trial, the exploration of novel SOS1 targeting strategies with distinct modes of action remains required. By employing proteolysis targeting chimera (PROTAC) technology, we obtained a series of new SOS1 degraders. The representative compound LHF418 potently induced SOS1 degradation with a DC50 value of 209.4 nM and a Dmax value of over 80 %. Mechanistic studies have illuminated that compound LHF418 induced the formation of ternary complex involving SOS1-PROTAC-cereblon (CRBN) and triggered SOS1 protein degradation in a CRBN- and proteasomedependent manner. In addition, compound LHF418 effectively inhibited KRAS-RAF-ERK signalling, leading to the suppression of colony formation in KRAS-driven cancer cells. Overall, compound LHF418 represents a new lead compound in the developing novel and potent therapy for the treatment of KRAS-driven cancers.

To address the contribution oftranscriptional regulation to Drosophila clock gene expression and to behavior, we generated a series of CRISPR- mediated deletions within two regions of the circadian gene timeless (tim), an intronic E - box region and an upstream E - box region that are both recognized by the key transcription factor Clock (Clk) and its heterodimeric partner Cycle. The upstream deletions but not an intronic deletion dramatically impact tim expression in fly heads; the biggest upstream deletion reduces peak RNA levels and tim RNA cycling amplitude to about 15% of normal, and there are similar effects on tim protein (TIM). The cycling amplitude of other clock genes is also strongly reduced, in these cases due to increases in trough levels. These data underscore the important contribution of the upstream E - box enhancer region to tim expression and of TIM to clock gene transcriptional repression in fly heads. Surprisingly, tim expression in clock neurons is only modestly affected by the biggest upstream deletion and is similarly affected by a deletion of the intronic E - box region. This distinction between clock neurons and glia is paralleled by a dramatically enhanced accessibility of the intronic enhancer region within clock neurons. This distinctive feature of tim chromatin was revealed by ATAC-seq (assay for transposase- accessible chromatin with sequencing) assays of purified neurons and glia as well as of fly heads. The enhanced cell type-specific accessibility of the intronic enhancer region explains the resilience of clock neuron tim expression and circadian behavior to deletion of the otherwise more prominent upstream tim E - box region. Significance Drosophila circadian rhythms are governed by a feedback loop, in which the positive transcription factor CLK (CLOCK)/CYC (CYCLE) associates with two E - box- containing enhancers, one upstream and one intronic, within its negative regulatory gene timeless. Reporter gene experiments from more than 20 y ago showed that only the upstream enhancer affects timeless expression in tissue culture and fly heads. Consistent with these observations are current experiments indicating that the upstream enhancer is essential for timeless expression in glia. However, these deletions only modestly affect clock neuron timeless expression and circadian behavior. ATAC- seq experiments show that the intronic enhancer is much more active in neurons than glia, which indicate a discrete regulatory program for core clock genes in circadian neurons.