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Cancer genome sequencing consortiums have recently catalogued an abundance of somatic mutations, across a wide range of human cancers, in the chromatin-modifying enzymes that regulate gene expression. Defining the molecular mechanisms underlying the potentially oncogenic functions of these epigenetic mutations could serve as the basis for precision medicine approaches to cancer therapy. MLL4 encoded by the KMT2D gene highly mutated in a large number of human cancers, is a key histone lysine monomethyltransferase within the Complex of Proteins Associated with Set1 (COMPASS) family that regulates gene expression through enhancer function, potentially functioning as a tumor suppressor. We report that the KMT2D mutations which cause MLL4 protein truncation also alter MLL4's subcellular localization, resulting in loss-of-function in the nucleus and gain-of-function in the cytoplasm. We demonstrate that isogenic correction of KMT2D truncation mutation rescues the aberrant localization phenotype and restores multiple regulatory functions of MLL4, including COMPASS integrity/stabilization, histone H3K4 mono-methylation, enhancer activation, and therefore transcriptional regulation. Moreover, isogenic correction diminishes the sensitivity of KMT2D-mutated cancer cells to targeted metabolic inhibition. Using immunohistochemistry, we identified that cytoplasmic MLL4 is unique to the tissue of bladder cancer patients with KMT2D truncation mutations. Using a preclinical carcinogen model of bladder cancer in mouse, we demonstrate that truncated cytoplasmic MLL4 predicts response to targeted metabolic inhibition therapy for bladder cancer and could be developed as a biomarker for KMT2D-mutated cancers. We also highlight the broader potential for prognosis, patient stratification and treatment decision-making based on KMT2D mutation status in MLL4 truncation-relevant diseases, including human cancers and Kabuki Syndrome. [ABSTRACT FROM AUTHOR]

The cross-cultural adaptation of social-emotional learning (SEL) has cast doubts. Although there are significant differences between low- and high-context cultures, fewanalyses have been conducted on the effects of SEL intervention in high-context cultures. To explore the effectiveness of the SEL program in China, which is different from low-context cultural background, this study presents findings from a meta-analysis of 86 randomized SEL programs involving 8,736 students. Compared with the control group, SEL participants significantly improved social-emotional competence (SEC), including SEL skills, attitudes, positive social behavior, and emotional distress (reduction). However, there was no significant improvement in behavioral problems. Due to the lack of emotional education in China and the Hawthorne effect, compared with SEL programs in low-context countries, China's SEL programs have improved SEC more, up to three times that of low-context countries. The general area of the school, SEL framework, intervention object, and educational level of participants moderates SEL positive outcomes. Types of textbooks, SEL framework, participant features, and educational level of participants moderate SEL negative outcomes. These findings provide empirical evidence for the positive impact of SEL programs in China. To improve the SEC of Chinese students, policymakers should actively implement SEL programs in China. [ABSTRACT FROM AUTHOR]

This paper presents an integrated multi-attribute decision-making (MADM) approach to aid selection of commercially available materials in the context of sustainable design. The MADM couples grey relational analysis (GRA) with an analytic hierarchy process (AHP) to rank alternative materials in terms of their economic, environmental, and social performance. AHP is used to determine the corresponding weighting values for the selected indicators. In addition, a case example is used to verify the proposed MADM method and demonstrate its practical application. Three alternative polymer materials, i.e., poly(vinyl chloride) (PVC), polypropylene (PP), and polyethylene (PE), are examined to determine their sustainability for plastic pipe design. The associated MADM result and the limitations of the approach are discussed to lay the foundation for further improvement. [ABSTRACT FROM AUTHOR]

Purpose - The purpose of this paper is to investigate the mediating effect of organizational trust on the relationship between perceived corporate social responsibility (CSR) practices and firm performance. Design/methodology/approach - A total of 674 questionnaires were sent randomly to Chinese firms to obtain a total of 168 reliable responses. A confirmatory factor analysis was conducted for a validity test, and structural equation modeling was employed to test the mediating effect of organizational trust. Findings - The empirical results show that perceived CSR practices of firms had significant direct effects on employee well-being and organizational performance and that organizational trust partially mediated the relationships of CSR practices to employee well-being as well as to organizational performance. Research limitations/implications - The data may not fully represent a generalized survey of all industries with CSR management. In this regard, future research should focus on a specific Chinese industry. The results suggest that firms should more actively promote the role of employees in CSR strategies to better build organizational trust. Originality/value - Previous CSR studies have generally focused on customers' perceptions, paying little attention to employees' viewpoints. This study provides the first empirical analysis of the relationship between CSR and firm performance from the perspective of employees in Chinese firms. In addition, the study examines the mediating role of trust in CSR, which has been rarely considered in the context of Chinese firms. [ABSTRACT FROM AUTHOR]

Most previous studies on corporate sustainability (corporate social responsibility) practices tend to focus on external stakeholders and outcomes. However, the influence of CSR practices on employees remains largely unexplored. In this study, we examine the influence of CSR practices on employees' attitudes and behaviors. We investigate the mediation effect of employees' attitudes and behaviors on the relationship between CSR practices and organizational performance. The empirical results indicate that employees' perceptions of CSR practices have a positive impact on their organizational commitment and organizational citizenship behavior. The organizational citizenship behavior partially mediates the relationship between CSR practices and organizational performance, whereas organizational commitment indirectly mediates the relationship only through organizational citizenship behavior. This study also raises some important implications based on the empirical results. [ABSTRACT FROM AUTHOR]