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Honokiol is a natural product with an interesting array of biological effects, including significant anti-tumor properties. However, full exploration of its therapeutic potential is hampered by its modest pharmacokinetic profile and by the lack of synthetic methods that allow to obtain specifically designed derivatives with improved properties. In addition, the specific molecular targets of honokiol remain poorly understood, a fact that limits the search of alternative hits for subsequent optimization programs. In this work we describe an optimized series of synthetic routes that allow to access to a variety of honokiol derivatives, including a set of minimalist photoaffinity probes to map potential protein targets in live cells. Chemical proteomic studies of the most potent probe revealed a defined set of proteins as the cellular targets of honokiol. Significantly, up to the 62 % of the identified proteins have described roles in cancer, highlighting their potential relationship with the antitumor effects of honokiol. Furthermore, several of the top hits have been validated as direct binding partners of honokiol by cellular thermal shift assay (CETSA). In sum, the work described herein provides the first landscape of the cellular targets of honokiol in living cells and contributes to define the specific molecular pathways affected by this natural product., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Silvia Ortega-Gutierrez reports financial support was provided by Ministerio de Ciencia e Innovacion. Daniel Fernandez reports financial support was provided by Comunidad de Madrid. Benjamin F. Cravatt reports financial support was provided by National Institutes of Health. Roman Foronda reports financial support was provided by Comunidad de Madrid. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Rib cage remodeling has shown promising aesthetic results as a new technique for body contouring, and yet risks and complications associated with the procedure have not been well established. The aim of the authors' study was to assess safety, efficacy, and patient satisfaction rate associated with a new surgical technique for waistline definition., Methods: The authors looked into their records for patients who underwent waist narrowing through a new rib remodeling procedure with osteosynthesis of ribs XI and XII from October of 2022 to June of 2023. Follow-up was carried out at 1 and 3 months after surgery. Outcomes were evaluated based on waist and hip measurements, body image, pain, and a patient satisfaction survey., Results: A total of 27 consecutive patients were included in the analysis. The authors' technique resulted in a significant reduction in waist circumference, as evidenced by a decrease of 12.1 cm and 13.0 cm at the first and third months, respectively ( P < 0.005). A reduction of hip circumference of 6.2 cm and 8.7 cm at the first and third months, respectively, was also reported. A high patient satisfaction rate was reported. Postoperative complications included only 1 case of wound dehiscence and 1 case of mild pain. Pain levels were also reduced, with a mean pain score of 2.4 at week 1 and 0.26 at month 1., Conclusions: Rib osteotomy with osteosynthesis emerges as an innovative, safe, and reliable approach for waist narrowing. The authors' results suggest that this technique can be applied to a wide variety of patients, and it might entail significant advantages compared with other techniques., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)