The work reports the progress of small-fluorescent molecules for bioimaging applications to cancer-relevant biomarkers H⁺, NO, H₂S and reactive oxygen species (H₂O₂, HClO, O₂˙⁻, ¹O₂ and ˙OH) over the past six years.

The synthesis and structure-activity relationship (SAR) studies of praziquantel derivatives with activity against adult Schistosoma japonicum are described. Several of them showed better worm killing activity than praziquantel and could serve as leads for further optimization.

Objective: Distant metastasis (DM) is an important prognostic factor in differentiated thyroid cancer (DTC) and determines the course of treatment. This study aimed to establish a predictive nomogram model that could individually estimate the risk of DM and analyze the prognosis of female DTC patients (FDTCs).Materials and methods: A total of 26,998 FDTCs were retrospectively searched from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 and randomly divided into validation and training cohorts. Univariate and multivariate analyses were performed to screen for prognostic factors and construct a prediction nomogram. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), concordance index (C-index), and a calibration curve. The overall survival (OS) and cancer-specific survival (CSS) were evaluated by Kaplan–Meier (K-M) analysis.Results: A total of 263 (0.97%) FDTCs were reported to have DM. K-M analysis showed the association of multiple-organ metastases and brain involvement with lower survival rates (P < 0.001) in patients. Tumor size, age at diagnosis, thyroidectomy, N1 stage, T3–4 stage, and pathological type were independent predictive factors of DM in FDTCs (all P < 0.001). Similarly, age at diagnosis, Black, DM, T3–4 stage, thyroidectomy, and lung metastasis were determined as independent prognostic factors for FDTCs (all P < 0.001). Several predictive nomograms were established based on the above factors. The C-index, AUC, and calibration curves demonstrated a good performance of these nomogram models.Conclusion: Our study was successful in establishing and validating nomograms that could predict DM, as well as CSS and OS in individual patients with FDTC based on a large study cohort. These nomograms could enable surgeons to perform individualized survival evaluation and risk stratification for FDTCs.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is overexpressed and/or overactivated in many human cancers and has been shown to play a critical role during oncogenesis. Despite the potential of Pin1 as a drug target, its successful targeting has proved to be challenging. We speculate that only blocking the enzymatic function of Pin1 with inhibitors may not be sufficient to lead to a total loss-of-function. Here, we report the discovery of P1D-34, a first-in-class and potent PROTAC degrader of Pin1, which induced Pin1 degradation with a DC₅₀ value of 177 nM and exhibited potent degradation-dependent anti-proliferative activities in a panel of acute myeloid leukemia (AML) cell lines. In contrast, Pin1 inhibitor Sulfopin did not show activity. More significantly, P1D-34 could sensitize Bcl-2 inhibitor ABT-199 in Bcl-2 inhibitor-resistant AML cells, highlighting the potential therapeutic value of targeted Pin1 degradation for Bcl-2 inhibitor-resistant AML treatment. Further mechanism study revealed that P1D-34 led to the up-regulation of ROS pathway and down-regulation of UPR pathway to induce cell DNA damage and apoptosis. Notably, we further demonstrated that treatment with the combination formula of glucose metabolism inhibitor 2-DG and P1D-34 led to a notable synergistic anti-proliferative effect, further expanding its applicability. These data clearly reveal the practicality and importance of PROTAC as a preliminary tool compound suitable for assessment of Pin1-dependent pharmacology and a promising strategy for AML treatment.