Microphthalmia-associated transcription factor (MITF) is a transcription factor that plays a central role in the pathogenesis, progression, and drug resistance of malignant melanoma. However, MITF has historically been viewed as a challenging drug target, largely due to a lack of deep, well-defined pockets amenable to traditional small-molecule inhibition. In this study, we present the discovery of WZS0347, a first-in-class proteolysis targeting chimera (PROTAC) designed to target MITF for degradation. WZS0347 potently reduced MITF protein levels in several melanoma cell lines, including B16F10, A375 and GAK. Mechanistic investigation confirmed that the degradation was mediated by a cereblon-dependent ubiquitin-proteasome pathway. Consequently, WZS0347 treatment led to the downregulation of MITF downstream target genes and significantly inhibited cancer cell colony formation and migration capacity.

Structural isomers are critical analytes in the biological and chemical arenas. Despite the ability of tandem mass spectrometry to provide fragment ion information, their high structural similarity impedes confident identification. To address this, we developed a novel method leveraging energy-resolved mass spectrometry (ER-MS) of fragment ions generated by electron activation dissociation (EAD). EAD initiated rapid radical chain dissociation via electron excitation and removal mechanisms, delivering superior isomer discrimination compared to conventional collision-induced dissociation (CID). Subsequent energy-resolved analysis further enhanced the distinction by integrating these dissociation mechanisms. Our strategy employed a cosine-based multidimensional spectral similarity algorithm to visualize and quantify subtle spectral differences across multiple energies. This method successfully distinguished many types of isomers, such as linkage, composition, and conformation isomers in disaccharides and flavonoid glycosides and achieved 93.8% top-1 identification accuracy against an in-house library. When applied to pomelo peel and commercial beverages for key metabolite characterization, it provided 44.4-50.0% top-1 annotation accuracy across all detected interest features. These results demonstrate that the multidimensional similarity algorithm that combines EAD and ER-MS significantly advances the depth and accuracy of compound annotation.

BCBs (bicyclo[1.1.0]butanes) serve as useful building blocks in organic synthesis due to their unique reactivity caused by the ring-strain. Herein, a copper-catalyzed olefination with BCBs and alpha-diazo-esters is disclosed, which generates tetrasubstituted olefins in a moderate Z/E ratio and pure Z-isomers are isolated in moderate yields. The reaction enjoys advantages such as mild reaction conditions, simple reaction protocol, good functional group tolerance, and low catalyst loading. As for disubstituted BCBs, various aryl groups and an aliphatic group are well tolerated. The synthetic utility of the present method is showcased by several transformations, which furnish structurally diverse tetrasubstituted olefins.

This work focuses on the synthesis and application research of silicon-containing biferrocene derivatives grafted onto hydroxyl-terminated polybutadiene (HTPB), to address the issues of volatility and migration tendency of ferrocene combustion catalysts in solid rocket propellants, as well as the insufficient catalytic performance caused by low iron content in ferrocene-containing polymeric materials. Firstly, a template reaction was employed to optimize the hydrosilylation reaction conditions. In this part, 4-vinyl-1-cyclohexene was employed as substrate, and the ratio of substrate, solvent, reaction time, reaction temperature was optimized. Based on the optimized condition, ferrocene silane derivatives and HTPB were utilized as substrates to obtain HTPB grafted silicon-containing biferrocene compounds. Subsequently, the relationship of biferrocene silane loading and the iron contents as well as the grafting rate were investigated. As the result, three different HTPB grafted silicon-containing biferrocene combustion catalysts were obtained by grafting biferrocene silane derivatives on HTPB polymers through hydrosilylation reactions. The iron contents of above combustion catalysts were 10.7%, 11.9% and 14.1% respectively, which were higher than that of Butacene (8%). At the same time, its thermal stability and catalytic decomposition performance of ammonium perchlorate (AP) were tested. The combustion catalysts were mixed with ultrafine AP at a mass ratio of 5:95, then carefully ground it to uniformity. The solvent was evaporated during the grinding process. After grinding, a mixture of combustion catalyst and AP was obtained, and then differential scanning calorimetry (DSC) and thermogravimetric (TG) study were employed. The results demonstrated that the decomposition temperature of AP under catalytic conditions were reduced. The initial and final decomposition temperatures of AP were reduced after adding 5% biferrocene-containing HTPB, with the final decomposition temperature reduced by about 57 similar to 77 degrees C, and the high decomposition temperature reduced by 87.4 similar to 103.7 degrees C, which could catalyze the decomposition of AP efficiently. These above combustion catalysts might be utilized in HTPB solid rocket propellant in the future.

Mapping the spatial proteome signature within heterogeneous tissue microenvironment of clinical specimens offers unique insights into both physiological and pathological molecular phenotypes. However, to simultaneously visualize and discover these spatial proteome features is challenging. Herein, we introduce spatial visual proteomics (SVPro) which integrates single-cell proximity biotinylation coupled with fluorescence signal amplification via the trifunctional probe. This probe uniquely combines naphthylamine-mediated radical targeting, clickable fluorescence imaging, and biotinylation-facilitated proteome capture, enabling all three within a single tissue section. Strategic PEGylation and multivalent fluorescent conjugation of these probes improves labeling and visualization efficiency and specificity. SVPro allows cell-type proteomic profiling of neuronal subpopulations in distinct mouse brain regions and amyloid-beta plaques in mouse brain of Alzheimer's disease model. Notably, we identified and validated distinct marker proteins associated with amyloid-beta plaques deposited in different brain regions. SVPro therefore emerges as a robust and high-resolution spatial proteomics approach for simultaneously visualizing the spatial architecture and proteome landscapes of intact tissue microenvironment.