SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO−TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.

The first comprehensive survey of 7,025 Chinese primary schoolchildren found that 24% of respondents reported that they had sometimes physically bullied another child. When children observed school bullying, 56% said they immediately reported it to their teachers. Another 20% tried to stop the bullying by approaching the bullies. The study also identified factors associated with bullying. These included coming from an adverse psychosocial background and having more contact with violent values through association with deviant peers and exposure to the mass media. On the basis of the research findings, potential methods of bullying intervention are discussed.

Results showed that age was significantly associated with positive emotions and cognitive reappraisal. No difference was found in negative emotions and suppression between younger and older adults. Cognitive reappraisal partially mediated the effect of age on positive emotions. Findings of this study contribute to our understanding of the underlying mechanism of age variations in emotional experiences.

This exploratory study reports an empirical attempt to (1) establish inter‐scorer and parallel‐forms reliabilities as well as convergent validity of the Chinese version of the TTCT, (2) measure the level of fluency, flexibility, and originality in 10–12 year‐old Hong Kong children, and (3) compare the scores of the Hong Kong sample with those from other studies. The Figural and Verbal Forms A and B were administered. The overall results showed high inter‐rater reliability of the Chinese version of the Test. The parallel‐forms reliability between the Verbal Forms (P > 0.001) of the Test was higher than that between the Figural Forms (P > 0.05). The Hong Kong results on the Figural Test were generally higher than those obtained in Taiwan, Singapore, and USA, but slightly lower than the German results. This trend in the results was reversed on the Verbal Forms. The absence of sex differences on the TTCT was noted.

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Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route. Here, we describe the identification of STING agonist 15a, a cyclic dinucleotide structurally diversified from natural ligands with optimized properties for systemic intravenous (iv) administration. Our studies have shown that STING activation by 15a leads to an acute innate immune response as measured by cytokine secretion and adaptive immune response via activation of CD8+ cytotoxic T-cells, which ultimately provides robust antitumor efficacy.

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