Prediction of pedicled flap survival preoperatively by operating indocyanine green angiography at 1,450 nm wavelength: an animal model study.

Background: Predicting flap viability benefits patients by reducing complications and guides flap design by reducing donor areas. Due to varying anatomy, obtaining individual vascular information preoperatively is fundamental for designing safe flaps. Although indocyanine green angiography (ICGA) is a conventional tool in intraoperative assessment and postoperative monitoring, it is rare in preoperative prediction. Methods: ICGA was performed on 20 male BALB/c mice under five wavelengths (900/1,000/1,100, /1,250/1,450 nm) to assess vascular resolution after ICG perfusion. A "mirrored-L" flap model with three angiosomes was established on another 20 male BALB/c mice, randomly divided into two equal groups. In Group A, a midline between angiosomes II and III was used as a border. In Group B, the points of the minimized choke vessel caliber marked according to the ICG signal at 1,450 nm wavelength (ICG1450) were connected. Necrotic area calculations, pathohistological testing, and statistical analysis were performed. Results: The vascular structure was clearly observed at 1,450 nm wavelength, while the 900 to 1,100 nm failed to depict vessel morphology. Necrosis was beyond the borderline in 60% of Group A. Conversely, 100% of Group B had necrosis distal to the borderline. The number of choke vessels between angiosomes II and III was positively correlated with the necrotic area (%). The pathohistological findings supported the gross observation and analysis. Conclusion: ICG1450 can delineate the vessel structure in vivo and predict the viability of pedicled skin flaps using the choke vessel as the border between angiosomes.

Systematic Structural Modification of Squaraine Dye for Near-Infrared Window One and Two Multiplexed In Vivo Imaging and Photothermal Therapy.

Due to the wide application of reporter gene-related visible/NIR-I bioluminescent imaging, multiplexed fluorescence imaging across visible/NIR-I/NIR-II has excellent potential in biomedical research. However, in vivo multiplexed imaging applications across those regions have rarely been reported due to the lack of proper fluorophores. Herein, nine squaraine dyes, which exhibit diverse adsorption and emission wavelengths, were synthesized. Among them, water-soluble SQ 710-5k and SQ 905 were found to have significant absorption differences, which allowed the tumor and lymph nodes to be identified. Then, for the first time, six-channel multiplexed fluorescence imaging across visible/NIR-I/II was achieved by coordination with reporter gene-related bioluminescent phosphors. Additional research revealed that SQ 710-5k exhibited higher-quality blood vessels and tumor imaging in NIR-II. H-aggregates SQ 905 demonstrated a high photothermal conversion efficiency for photothermal therapy. This study proposed an approach to creating small molecular dyes that coordinate with reporter gene-related bioluminescent phosphors for six-color fluorescence imaging.

Hypsochromic Shift Donor-Acceptor NIR-II Dye for High-Efficiency Tumor Imaging.

Nowadays, second near-infrared window (NIR-II) dyes' development focuses on pursuing a longer absorption/emission wavelength and higher quantum yield, which usually means an extended π conjugation system, resulting in an enormous molecular weight and poor druggability. Most researchers thought that the reduced π conjugation system would bring on a blueshift spectrum that causes dim imaging qualities. Little efforts have been made to study smaller NIR-II dyes with a reduced π conjugation system. Herein, we synthesized a reduced π conjugation system donor-acceptor (D-A) probe TQ-1006 (Em = 1006 nm). Compared with its counterpart donor-acceptor-donor (D-A-D) structure TQT-1048 (Em = 1048 nm), TQ-1006 exhibited comparable excellent blood vessels, lymphatic drainage imaging performance, and a higher tumor-to-normal tissue (T/N) ratio. An RGD conjugated probe TQ-RGD showed an extra high contrast tumor imaging (T/N ≥ 10), further proving D-A dyes' excellent NIR-II biomedical imaging applications. Overall, the D-A framework provides a promising approach to designing next-generation NIR-II fluorophores.

Design, Synthesis and Biological Evaluation of Novel Benzoylimidazole Derivatives as Raf and Histone Deacetylases Dual Inhibitors.

In recent studies, combinations of histone deacetylases (HDACs) inhibitor with kinase inhibitor showed additive and synergistic effects. BRafV600E as an attractive target in many diseases treatments has been studied extensively. Herein, we present a novel design approach though incorporating the pharmacophores of BRafV600E inhibitor and HDACs inhibitor in one molecule. Several synthesized compounds exhibited distinct BRafV600E and HDAC1 inhibitory activities. The representative dual Raf/HDAC inhibitor, 7a, showed better antiproliferative activities against A549 and SK-Mel-2 in cellular assay than SAHA and sorafenib, with IC50 values of 9.11 µM and 5.40 µM, respectively. This work may lay the foundation for the further development of dual Raf/HDAC inhibitors as potential anticancer agents.

Copper-catalyzed diastereoselective synthesis of ß-boryl-α-quaternary carbon carboxylic esters.

Cu(i)-Catalyzed diastereoselective carboboration of α-alkyl-substituted α,ß-unsaturated carboxylic esters to produce ß-boryl-α-quaternary carbon esters was developed. The carbon skeletons of dialkyl sulfates, primary allyl halides, and benzyl bromides were transferred to the α-position of the substrates to provide products in moderate to good yields with a diastereoselectivity of >95% in most cases. Substrates bearing a ß-(hetero)aryl substituent gave higher diastereoselectivities than those bearing a linear ß-alkyl substituent. The crystal structure of the potassium trifluoroborate derivative shows that the reactions probably go through a copper(i) enolate intermediate and the diastereoselectivity arises from the electrophilic attack of electrophiles to the less hindered side of the enolates.