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Purpose: Ferroptosis, a programmed cell death modality, is an iron-dependent, non-apoptosis pathway that is characterized by the upregulation of divalent iron and reactive oxygen species (ROS) levels. However, the sensitive and rapid detection to track changes in ferroptosis is challenging, partially due to the lack of methods for monitoring the Fe(II) accumulation and ROS generation. Procedures: Herein, we reported a dual-reaction fluorescent probe DR-1 with turn-on response, which realized the simultaneous visualizing of Fe(II) and ROS with a single probe. The structure of fluorescence quenching group and turn-on fluorophore constitute a double switch for DR-1, which increases its specificity and stability. Results: During ferroptotic cell death, the upregulation of ROS levels led to the cleavage of quenching group of DR-1, and the aggregation of Fe(II) resulting in fluorescence recovery. Conclusions: Overall, this study provides a new dual-reaction probe that shows the great potential to explore the mechanism of ferroptosis in vitro and in vivo by fluorescence imaging. [ABSTRACT FROM AUTHOR]

Background: With the improvement in diagnostic imaging, perioperative care and surgical technique, the indications and complexity of liver resections have developed. However, the surgical indications remain controversial especially for some complex or advanced hepatocellular carcinomas. This study was designed to evaluate the concordance between hepatectomy recommendations proposed by Watson for Oncology, a cognitive technology providing decision support, and those determined by surgeons in our center for patients with hepatocellular carcinoma. Methods: We retrospectively reviewed 243 patients with hepatocellular carcinoma who were recommended for surgical treatment and received hepatectomy between 2008 and 2016 at the Zhujiang Hospital of Southern Medical University. Watson for Oncology classified the treatment options into three categories: recommended, for consideration and not recommended. Treatment recommendations were considered concordant if the hepatectomy recommendations were designated "recommended" or "for consideration" by Watson for Oncology. The factors potentially affecting concordance rate were also analyzed in our study. Results: The hepatectomy recommendations of 174 patients were concordant. There were significant differences in the coincidence rate between concordant group and discordant group considering tumor numbers (P = 0.006), extension of hepatectomy (P = 0.009) and BCLC staging system (P < 0.001). Lower degrees of concordance were observed in patients with multiple tumors, major hepatectomy and portal hypertension by using logistic regression analysis (OR = 0.309, P = 0.004; OR = 0.384, P = 0.004; and OR = 0.376, P = 0.022, respectively). Conclusion: The concordance between Watson for Oncology and surgeons' hepatectomy recommendation for hepatocellular carcinoma was only 72%. Differences in practice patterns for HCC between the USA (where Watson for Oncology was calibrated) and China may be the major cause of discordance. Watson for Oncology still requires further improvement and localization to be widely applied in China. [ABSTRACT FROM AUTHOR]

Crossing over is essential for chromosome segregation during meiosis. Protein modification by SUMO is implicated in crossover control, but pertinent targets have remained elusive. Here we identify Msh4 as a target of SUMO-mediated crossover regulation. Msh4 and Msh5 constitute the MutSγ complex, which stabilizes joint-molecule (JM) recombination intermediates and facilitates their resolution into crossovers. Msh4 SUMOylation enhances these processes to ensure that each chromosome pair acquires at least one crossover. Msh4 is directly targeted by E2 conjugase Ubc9, initially becoming mono-SUMOylated in response to DNA double-strand breaks, then multi/poly-SUMOylated forms arise as homologs fully engage. Mechanistically, SUMOylation fosters interaction between Msh4 and Msh5. We infer that initial SUMOylation of Msh4 enhances assembly of MutSγ in anticipation of JM formation, while secondary SUMOylation may promote downstream functions. Regulation of Msh4 by SUMO is distinct and independent of its previously described stabilization by phosphorylation, defining MutSγ as a hub for crossover control. [Display omitted] • Crossover factor Msh4 is a direct target of the SUMO E2-conjugase Ubc9 • Msh4 SUMOylation facilitates meiotic crossing over • SUMOylation fosters interaction between Msh4 and Msh5 • Msh4 SUMOylation is triggered by DNA double-strand breaks Meiotic crossovers promote accurate chromosome segregation. He et al. show that SUMO modifies the recombination factor Msh4, enhancing its interaction with Msh5 to assemble the MutSγ complex, which promotes crossovers. Msh4 SUMOylation requires DNA double-strand breaks, defining a pathway that couples the initiation of recombination to crossover control. [ABSTRACT FROM AUTHOR]